Journal of Pathology and Translational Medicine

Case Study

Colorectal cancer with a germline BRCA1 variant inherited paternally: a case report: Kyoung Min Kim, Min Ro Lee, Ae Ri Ahn, Myoung Ja Chung; J Pathol Transl Med. 2024;58(6):341-345. Published online September 5, 2024; DOI: https://doi.org/10.4132/jptm.2024.08.14

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Abstract PDF: BRCA genes have well-known associations with breast and ovarian cancers. However, variations in the BRCA gene, especially germline variations, have also been reported in colorectal cancer (CRC). We present the case of a rectal cancer with a germline BRCA1 variation inherited from the paternal side. A 39-year-old male was admitted with rectal cancer. The patient underwent surgical resection and the pathologic diagnosis was adenocarcinoma. Next-generation sequencing was performed and a BRCA1 variant was detected. Reviewing the public database and considering the young age of the patient, the variant was suggested to be germline. The patient’s father had had prostate cancer and next-generation sequencing testing revealed an identical BRCA1 variant. In the BRCA cancer group, there is relatively little attention paid to male cancers. The accumulation of male CRC cases linked to BRCA variations may help clarify the potential pathological relationship between the two.

Original Articles

The spectrum of microvascular patterns in adult diffuse glioma and their correlation with tumor grade: Soni , Vaishali Walke, Deepti Joshi, Tanya Sharma, Adesh Shrivastava, Amit Agrawal; J Pathol Transl Med. 2024;58(3):127-133. Published online May 14, 2024; DOI: https://doi.org/10.4132/jptm.2024.03.11

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Background
Primary brain tumors constitute the leading cause of cancer-related mortality. Among them, adult diffuse gliomas are the most common type, affecting the cerebral hemispheres and displaying a diffuse infiltrative pattern of growth in the surrounding neuropil that accounts for about 80% of all primary intracranial tumors. The hallmark feature of gliomas is blood vessel proliferation, which plays an important role in tumor growth, tumor biological behavior, and disease outcome. High-grade gliomas exhibit increased vascularity, the worst prognosis, and lower survival rates. Several angiogenic receptors and factors are upregulated in glioblastomas and stimulate angiogenesis signaling pathways by means of activating oncogenes and/or down-regulating tumor-suppressor genes. Existing literature has emphasized that different microvascular patterns (MVPs) are displayed in different subtypes of adult diffuse gliomas.
Methods
We examined the distribution and biological characteristics of different MVPs in 50 patients with adult diffuse gliomas. Haematoxylin and eosin staining results, along with periodic acid–Schiff and CD34 dual-stained sections, were examined to assess the vascular patterns and correlate with different grades of diffuse glioma.
Results
The present observational study on adult diffuse glioma evaluated tumor grade and MVPs. Microvascular sprouting was the most common pattern, while a bizarre pattern (type 2) was associated with the presence of a high-grade glioma. Vascular mimicry was observed in 6% of cases, all of which were grade 4 gliomas.
Conclusions
This study supplements the role of neo-angiogenesis and aberrant vasculature patterns in the grading and progression of adult diffuse gliomas, which can be future targets for planning treatment strategies.

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BRCA-mutated gastric adenocarcinomas are associated with chromosomal instability and responsiveness to platinum-based chemotherapy: Ji Hyun Oh, Chang Ohk Sung, Hyung-Don Kim, Sung-Min Chun, Jihun Kim; J Pathol Transl Med. 2023;57(6):323-331. Published online November 14, 2023; DOI: https://doi.org/10.4132/jptm.2023.10.22

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Abstract PDF Supplementary Material

Background
Homologous recombination defect is an important biomarker of chemotherapy in certain tumor types, and the presence of pathogenic or likely pathogenic mutations involving BRCA1 or BRCA2 (p-BRCA) mutations is the most well-established marker for the homologous recombination defect. Gastric cancer, one of the most prevalent tumor types in Asia, also harbors p-BRCA mutations.
Methods
To investigate the clinical significance of p-BRCA mutations, we analyzed 366 gastric cancer cases through next-generation sequencing. We determined the zygosity of p-BRCA mutations based on the calculated tumor purity through variant allelic fraction patterns and investigated whether the presence of p-BRCA mutations is associated with platinum-based chemotherapy and a certain molecular subtype.
Results
Biallelic p-BRCA mutation was associated with better response to platinum-based chemotherapy than heterozygous p-BRCA mutation or wild type BRCA genes. The biallelic p-BRCA mutations was observed only in the chromosomal instability subtype, while all p-BRCA mutations were heterozygous in microsatellite instability subtype.
Conclusions
In conclusion, patients with gastric cancer harboring biallelic p-BRCA mutations were associated with a good initial response to platinum-based chemotherapy and those tumors were exclusively chromosomal instability subtype. Further investigation for potential association with homologous recombination defect is warranted.

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Review

Clinicopathological characteristics of BRCA-associated breast cancer in Asian patients: Eun-Kyu Kim, So Yeon Park, Sung-Won Kim; J Pathol Transl Med. 2020;54(4):265-275. Published online May 14, 2020; DOI: https://doi.org/10.4132/jptm.2020.04.07

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Abstract PDF

BRCA1/2 germline mutations account for the majority of hereditary breast cancers. Since the identification of the BRCA genes, several attempts have been made to define the clinicopathological characteristics of BRCA-associated breast cancer in comparison with sporadic breast cancer. Asians constitute 60% of the world population, and although the incidence of breast cancer in Asia remains low compared to the West, breast cancer is the most prevalent female cancer in the region. The epidemiological aspects of breast cancer are different between Asians and Caucasians. Asian patients present with breast cancer at a younger age than Western patients. The contributions of BRCA1/2 mutations to breast cancer incidence are expected to differ between Asians and Caucasians, and the different genetic backgrounds among races are likely to influence the breast cancer phenotypes. However, most large-scale studies on the clinicopathological characteristics of BRCA-associated breast cancer have been on Western patients, while studies on Asian populations were small and sporadic. In this review, we provide an overview of the clinical and pathological characteristics of BRCA-associated breast cancer, incorporating findings on Asian patients.

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Original Article

Implication of PHF2 Expression in Clear Cell Renal Cell Carcinoma: Cheol Lee, Bohyun Kim, Boram Song, Kyung Chul Moon; J Pathol Transl Med. 2017;51(4):359-364. Published online June 13, 2017; DOI: https://doi.org/10.4132/jptm.2017.03.16

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Abstract PDF

Background
Clear cell renal cell carcinoma (CCRCC) is presumed to be associated with adipogenic differentiation. Histone modification is known to be important for adipogenesis, and the function of histone demethylase plant homeodomain finger 2 (PHF2) has been noted. In addition, PHF2 may act as a tumor suppressor via epigenetic regulation of p53 and is reported to be reduced in colon cancer and stomach cancer tissues. In this study, we examined PHF2 expression in CCRCC specimens by immunohistochemistry.
Methods
We studied 254 CCRCCs and 56 non-neoplastic renal tissues from patients who underwent radical or partial nephrectomy between 2000 and 2003 at the Seoul National University Hospital. Tissue microarray blocks were prepared, and immunohistochemical staining for PHF2 was performed.
Results
Among 254 CCRCC cases, 150 cases (59.1%) showed high expression and 104 cases (40.1%) showed low expression. High expression of PHF2 was significantly correlated with a low Fuhrman nuclear grade (p < .001), smaller tumor size (p < .001), low overall stage (p = .003), longer cancer-specific survival (p = .002), and progression-free survival (p < .001) of the patients. However, it was not an independent prognostic factor in multivariate analysis adjusted for Fuhrman nuclear grade and overall stage.
Conclusions
Our study showed that low expression of PHF2 is associated with aggressiveness and poor prognosis of CCRCC.

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Reviews

Pathology-MRI Correlation of Hepatocarcinogenesis: Recent Update: Jimi Huh, Kyung Won Kim, Jihun Kim, Eunsil Yu; J Pathol Transl Med. 2015;49(3):218-229. Published online May 15, 2015; DOI: https://doi.org/10.4132/jptm.2015.04.15

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Abstract PDF

Understanding the important alterations during hepatocarcinogenesis as well as the characteristic magnetic resonance imaging (MRI) and histopathological features will be helpful for managing patients with chronic liver disease and hepatocellular carcinoma. Recent advances in MRI techniques, such as fat/iron quantification, diffusion-weighted images, and gadoxetic acid-enhanced MRI, have greatly enhanced our understanding of hepatocarcinogenesis.

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Molecular Imaging in the Era of Personalized Medicine: Kyung-Ho Jung, Kyung-Han Lee; J Pathol Transl Med. 2015;49(1):5-12. Published online January 15, 2015; DOI: https://doi.org/10.4132/jptm.2014.10.24

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Abstract PDF

Clinical imaging creates visual representations of the body interior for disease assessment. The role of clinical imaging significantly overlaps with that of pathology, and diagnostic workflows largely depend on both fields. The field of clinical imaging is presently undergoing a radical change through the emergence of a new field called molecular imaging. This new technology, which lies at the intersection between imaging and molecular biology, enables noninvasive visualization of biochemical processes at the molecular level within living bodies. Molecular imaging differs from traditional anatomical imaging in that biomarkers known as imaging probes are used to visualize target molecules-of-interest. This ability opens up exciting new possibilities for applications in oncologic, neurological and cardiovascular diseases. Molecular imaging is expected to make major contributions to personalized medicine by allowing earlier diagnosis and predicting treatment response. The technique is also making a huge impact on pharmaceutical development by optimizing preclinical and clinical tests for new drug candidates. This review will describe the basic principles of molecular imaging and will briefly touch on three examples (from an immense list of new techniques) that may contribute to personalized medicine: receptor imaging, angiogenesis imaging, and apoptosis imaging.

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Original Articles

Evaluation of Protein Expression in Housekeeping Genes across Multiple Tissues in Rats: Hye Jeong Kim, Jong In Na, Byung Woo Min, Joo Young Na, Kyung Hwa Lee, Jae Hyuk Lee, Young Jik Lee, Hyung Seok Kim, Jong Tae Park; Korean J Pathol. 2014;48(3):193-200. Published online June 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.3.193

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Abstract PDF

Background

Housekeeping genes, which show constant protein expression patterns between different tissue types, are very important in molecular biological studies as an internal control for protein research.

Methods

The protein expression profiles of seven housekeeping genes (HPRT1, PPIA, GYS1, TBP, YWHAZ, GAPDH and ACTB) in various rat tissues (cerebrum, cerebellum, cardiac ventricle and atrium, psoas muscle, femoral muscle, liver, spleen, kidney, and aorta) were analyzed by Western blot and compared by coefficient of variation (CV).

Results

HPRT1 was stably expressed (CV≤10%) in six tissues (cerebrum, cerebellum, ventricle, femoral muscle, spleen, and kidney), PPIA was stably expressed in five tissues (cerebrum, cerebellum, ventricle, spleen and kidney), YWHAZ was stably expressed in three tissues (cerebrum, cerebellum, and kidney), and GAPDH was stably expressed in four tissues (cerebrum, ventricle, psoas muscle, and kidney). In comparison, GYS1, TBP, and ACTB were found to have CV values over 10% in all tissues. Of the seven genes examined, four (HPRT1, PPIA, YWHAZ, and GAPDH) were found to be stably expressed across multiple organs, with low CV values (≤10%).

Conclusions

These results will provide fundamental information regarding internal controls for protein expression studies and can be used for analysis of postmortem protein degradation patterns in forensic medicine.

Citations

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Uncommon and Rare Human Papillomavirus Genotypes Relating to Cervical Carcinomas: Na Rae Kim, Myunghee Kang, Soon Pyo Lee, Hyunchul Kim, Jungsuk An, Dong Hae Chung, Seung Yeon Ha, Hyun Yee Cho; Korean J Pathol. 2014;48(1):43-49. Published online February 25, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.43

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Abstract PDF

Background

Human papillomavirus (HPV) is an oncogenic virus in cervical cancer and most invasive carcinomas (ICs) are caused by HPV16 and 18. However, the roles and contributions of other uncommon and rare genotypes remain uncertain.

Methods

HPV genotypes were retrospectively assessed using an HPV DNA chip that can specify up to 32 HPV genotypes. We arbitrarily regarded genotypes accounting for less than 6% of the total as uncommon and rare genotypes.

Results

A total of 3,164 HPV-positive cases were enrolled. In groups 2A, 2B, 3, and unclassified HPV genotypes, 2.4% of cases with uncommon HPV genotypes (68, 26, 34, 53, 66, 69, 70, 73, 40, 42, 43, 44, 54, 55, 61, 62, 6, and 11) showed high grade squamous intraepithelial lesions and ICs. There were no HPV32- and 57-infected cases.

Conclusions

We found that the uncommon and rare HPV genotypes may provide incremental etiologic contributions in cervical carcinogenesis, especially HPV68, 70, and 53. Further studies on these uncommon and rare HPV genotypes will be of importance in establishing the significance of genotypes in different regions, especially in planning a strategy for further vaccine development as well as follow-up on the effectiveness of the currently used vaccines.

Citations

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High-risk human papillomavirus diversity among indigenous women of western Botswana with normal cervical cytology and dysplasia
Patricia S. Rantshabeng, Billy M. Tsima, Andrew K. Ndlovu, Keneilwe Motlhatlhedi, Kirthana Sharma, Carol B. Masole, Natasha O. Moraka, Kesego Motsumi, Angela K. T. Maoto-Mokote, Alemayehu B. Eshetu, Leabaneng Tawe, Tendani Gaolathe, Sikhulile Moyo, Lynnet
BMC Infectious Diseases.2024;[Epub] CrossRef
Human Papillomavirus (HPV69/HPV73) Coinfection associated with Simultaneous Squamous Cell Carcinoma of the Anus and Presumed Lung Metastasis
Stephanie Shea, Marina Muñoz, Stephen C. Ward, Mary B. Beasley, Melissa R Gitman, Michael D Nowak, Jane Houldsworth, Emilia Mia Sordillo, Juan David Ramirez, Alberto E. Paniz Mondolfi
Viruses.2020; 12(3): 349. CrossRef
Human Papillomavirus Selected Properties and Related Cervical Cancer Prevention Issues
Saule Balmagambetova, Andrea Tinelli, Ospan A. Mynbaev, Arip Koyshybaev, Olzhas Urazayev, Nurgul Kereyeva, Elnara Ismagulova
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Periungual Bowen's disease with a narrow longitudinal melanonychia mimicking periungual warts
Taiyo HITAKA, Michiko HASEGAWA, Akira SHIMIZU, Yuko KURIYAMA, Atsushi TAMURA
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Detection of HPV RNA molecules in stratified mucin-producing intraepithelial lesion (SMILE) with concurrent cervical intraepithelial lesion: a case report
Shiho Fukui, Kazunori Nagasaka, Naoko Iimura, Ranka Kanda, Takayuki Ichinose, Takeru Sugihara, Haruko Hiraike, Shunsuke Nakagawa, Yuko Sasajima, Takuya Ayabe
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Pitfalls of commercially available HPV tests in HPV68a detection
Hana Jaworek, Katerina Kubanova, Vladimira Koudelakova, Rastislav Slavkovsky, Jiri Drabek, Marian Hajduch, Craig Meyers
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Overall accuracy of cervical cytology and clinicopathological significance of LSIL cells in ASC‐H cytology
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Human papillomavirus genotyping by Linear Array and Next-Generation Sequencing in cervical samples from Western Mexico
María Guadalupe Flores-Miramontes, Luis Alberto Torres-Reyes, Liliana Alvarado-Ruíz, Salvador Angel Romero-Martínez, Verenice Ramírez-Rodríguez, Luz María Adriana Balderas-Peña, Verónica Vallejo-Ruíz, Patricia Piña-Sánchez, Elva Irene Cortés-Gutiérrez, Lu
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Impact of human papillomavirus coinfections on the risk of high-grade squamous intraepithelial lesion and cervical cancer
Adela Carrillo-García, Sergio Ponce-de-León-Rosales, David Cantú-de-León, Verónica Fragoso-Ontiveros, Imelda Martínez-Ramírez, Asunción Orozco-Colín, Alejandro Mohar, Marcela Lizano
Gynecologic Oncology.2014; 134(3): 534. CrossRef
Human papillomavirus 66‐associated subungual squamous cell carcinoma
Jin Hee Kang, Hwa young Ahn, Miri Kim, Shin Taek Oh, Baik Kee Cho, Hyun Jeong Park
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Primary Squamous Cell Carcinoma of the Upper Genital Tract: Utility of p16^INK4a Expression and HPV DNA Status in its Differential Diagnosis from Extended Cervical Squamous Cell Carcinoma: Su Hyun Yoo, Eun-Mi Son, Chang Okh Sung, Kyu-Rae Kim; Korean J Pathol. 2013;47(6):549-556. Published online December 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.549

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Abstract PDF

Background

Primary squamous cell carcinoma (SCC) of the upper genital tract, including the endometrium, fallopian tubes, and ovaries, is extremely rare. It must be distinguished from the mucosal extension of primary cervical SCC because determination of the primary tumor site is important for tumor staging. However, patients with SCC of the fallopian tubes or ovarian surface have often undergone prior hysterectomy with inadequate examination of the cervix, making it difficult to determine the primary site.

Methods

We compared histologic findings, p16^INK4a expression, and human papillomavirus (HPV) DNA status in four patients with primary SCC of the upper genital tract and five patients with primary cervical SCC extending to the mucosa of the upper genital tract.

Results

All five SCCs of cervical origin showed strong expression of p16^INK4a, whereas all four SCCs of the upper genital tract were negative, although one showed weak focal staining. Three of the five cervical SCCs were positive for HPV16 DNA, whereas all four primary SCCs of the upper genital tract were negative for HPV DNA.

Conclusions

Although a thorough histological examination is important, immunonegativity for p16^INK4a and negative for HPV DNA may be useful adjuncts in determining primary SCCs of the upper genital tract.

Citations

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Shoichi Sakamoto, Yuki Yamamoto, Michihiro Takiwaki, Yumi Nakantani, Seiji Kanno, Yoshimasa Mera, Masazumi Tanigami, Yusuke Inada, Yutaka Inaba, Kayo Kunimoto, Hiroshi Yamada, Yoshifumi Iwahashi, Shin‐ichi Murata, Masatoshi Jinnin
Australasian Journal of Dermatology.2025; 66(3): 175. CrossRef
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Daniela Fanni, Michele Peiretti, Valerio Mais, Elena Massa, Clara Gerosa, Francesca Ledda, Maria Luisa Fais, Gavino Faa, Stefano Angioni
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Molecular Analysis of HPV-independent Primary Endometrial Squamous Cell Carcinoma Reveals TP53 and CDKN2A Comutations
Mark R. Hopkins, Doreen N. Palsgrove, Brigitte M. Ronnett, Russell Vang, Jeffrey Lin, Tricia A. Murdock
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U. Kellner, A. Kellner, U. Cirkel
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Immunohistochemical Classification of Primary and Secondary Glioblastomas: Kyu Sang Lee, Gheeyoung Choe, Kyung Han Nam, An Na Seo, Sumi Yun, Kyung Ju Kim, Hwa Jin Cho, Sung Hye Park; Korean J Pathol. 2013;47(6):541-548. Published online December 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.541

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69 Download
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Abstract PDF

Background

Glioblastomas may develop de novo (primary glioblastomas, P-GBLs) or through progression from lower-grade astrocytomas (secondary glioblastomas, S-GBLs). The aim of this study was to compare the immunohistochemical classification of glioblastomas with clinically determined P-GBLs and S-GBLs to identify the best combination of antibodies for immunohistochemical classification.

Methods

We evaluated the immunohistochemical expression of epidermal growth factor receptor (EGFR), p53, and isocitrate dehydrogenase 1 (IDH-1) in 150 glioblastoma cases.

Results

According to clinical history, the glioblastomas analyzed in this study consisted of 146 P-GBLs and 4 S-GBLs. Immunohistochemical expression of EGFR, p53, and IDH-1 was observed in 62.6%, 49.3%, and 11.1%, respectively. Immunohistochemical profiles of EGFR(+)/p53(-), IDH-1(-)/EGFR(+)/p53(-), and EGFR(-)/p53(+) were noted in 41.3%, 40.2%, and 28.7%, respectively. Expression of IDH-1 and EGFR(-)/p53(+) was positively correlated with young age. The typical immunohistochemical features of S-GBLs comprised IDH-1(+)/EGFR(-)/p53(+), and were noted in 3.6% of clinically P-GBLs. The combination of IDH-1(-) or EGFR(+) was the best set of immunohistochemical stains for identifying P-GBLs, whereas the combination of IDH-1(+) and EGFR(-) was best for identifying S-GBLs.

Conclusions

We recommend a combination of IDH-1 and EGFR for immunohistochemical classification of glioblastomas. We expect our results to be useful for determining treatment strategies for glioblastoma patients.

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Egyptian Journal of Pathology.2016; 36(2): 282. CrossRef

Case Study

Peripheral Primitive Neuroectodermal Tumor with Osseous Component of the Small Bowel Mesentery: A Case Study: Joon Mee Kim, Young Chae Chu, Chang Hwan Choi, Lucia Kim, Suk Jin Choi, In Suh Park, Jee Young Han, Kyung Rae Kim, Yoon-La Choi, Taeeun Kim; Korean J Pathol. 2013;47(1):77-81. Published online February 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.77

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Abstract PDF

A case of peripheral primitive neuroectodermal tumor of the small bowel mesentery with osseous component is reported. A 23-year-old man was admitted to our hospital because of acute severe abdominal pain. Abdominal computed tomography revealed a large solid and cystic, oval shaped mass, measuring 11.0×6.0 cm in the pelvic cavity. Histologically the resected lesion consisted of sheets of undifferentiated small round cells forming Homer-Wright rosettes and perivascular pseudorosettes, and showed areas of osteoid and bone formation. Immunohistochemical studies revealed that tumor cells expressed positivity against CD99 (MIC2), CD57, neuron-specific enolase, and vimentin. Fluorescence in situ hybridization study revealed Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangement on chromosome 22q12. To the authors' knowledge this is the first documentation of a peripheral neuroectodermal tumor with osteoid and bone formation of the small bowel mesentery.

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Dan Liu, Xiaoge Liu, Yan Deng, Ran Wu, Xin Li
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Baofa Luo, Wei Gao, Ting Li, Xinran Yu, Fei Guo
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Andrej Kolosov, Audrius Dulskas, Kastytis Pauza, Veslava Selichova, Dmitrij Seinin, Eugenijus Stratilatovas
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Case report and literature review of Ewing's sarcoma in the gastrointestinal tract
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Pediatric Ewing’s Sarcoma/Primitive Neuroectodermal Tumor (ES/PNET) Developed in the Small Intestine: A Case Report
You Sun Kim, Hye Min Moon, Kyu Sang Lee, Young Suk Park, Hyun-Young Kim, Ji Young Kim, Jin Min Cho, Hyoung Soo Choi
Clinical Pediatric Hematology-Oncology.2017; 24(2): 162. CrossRef
Huge peripheral primitive neuroectodermal tumor of the small bowel mesentery at nonage: A case report and review of the literature
Zhe Liu, Yuan-Hong Xu, Chun-Lin Ge, Jin Long, Rui-Xia Du, Ke-Jian Guo
World Journal of Clinical Cases.2016; 4(9): 306. CrossRef
Primary primitive neuroectodermal tumor arising in the mesentery and ileocecum: A report of three cases and review of the literature
LIBO PENG, LIMIN YANG, NAN WU, BO WU
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Une curieuse tumeur digestive à cellules rondes
Alia Zehani, Ines Chelly, Beya Chelly, Jean-Michel Coindre, Slim Haouet, Nidhameddine Kchir
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Case Report

Primary Endometrial Squamous Cell Carcinoma: A Case Report and Review of Relevant Literature on Korean Women: Sung Jong Lee, Hyun Joo Choi; Korean J Pathol. 2012;46(4):395-398. Published online August 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.4.395

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Abstract PDF

Primary endometrial squamous cell carcinoma (PESCC) is an extremely rare tumor with unclear pathogenesis. A 54-year-old postmenopausal woman presented with a 6-month history of vaginal bleeding. The patient was provisionally diagnosed with uterine submucosal leiomyoma. This was followed by total hysterectomy with a bilateral salpingo-oophorectomy under the laparoscopic guidance. Histopathologically, the tumor was PESCC which was accompanied by a lack of the tumor in the uterine cervix. The tumor showed positive immunoreactivity for p^16INK4a. But there was no evidence of human papillomavirus (HPV) on in situ hybridization and HPV DNA chip analysis. We also present a review of the relevant literature on Korean women.

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Primary squamous cell carcinoma of the uterine wall associated with adenomyosis: A rare case report and literature review
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International Journal of Gynecology & Obstetrics.2025;[Epub] CrossRef
p16 Block Type Overexpression, p53 Wild Type Reactivity, and Cervical Involvement do not Always Exclude the Diagnosis of Primary Endometrial Squamous Cell Carcinoma (PESCC)
Daniela Fanni, Clara Gerosa, Michele Peiretti, Valerio Mais, Elena Massa, Stefano Angioni, Gavino Faa
International Journal of Gynecological Pathology.2024; 43(2): 200. CrossRef
Pathogenetic characteristics of endometrioid adenocarcinoma of uterus at present stage
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Treatment of primary squamous cell carcinoma of the endometrium and review of previous literature: A case report
Liyun Song, Qi Wu, Suning Bai, Ren Xu, Xiaona Wang, Yanyan Yang
Medicine.2023; 102(17): e33667. CrossRef
Prevalence of human papilloma virus and Chlamydia trachomatis in endometrial and cervical carcinoma: a comparative study in North Indian women
Heena Gautam, Sumita Mehta, Nidhi Nayar, Neha Kumar, Syed Akhtar Husain, Mausumi Bharadwaj
Systems Biology in Reproductive Medicine.2023; 69(6): 399. CrossRef
PAX8 Positivity, Abnormal p53 Expression, and p16 Negativity in a Primary Endometrial Squamous Cell Carcinoma: A Case Report and Review of the Literature
Daniela Fanni, Michele Peiretti, Valerio Mais, Elena Massa, Clara Gerosa, Francesca Ledda, Maria Luisa Fais, Gavino Faa, Stefano Angioni
International Journal of Gynecological Pathology.2022; 41(4): 431. CrossRef
Molecular Analysis of HPV-independent Primary Endometrial Squamous Cell Carcinoma Reveals TP53 and CDKN2A Comutations
Mark R. Hopkins, Doreen N. Palsgrove, Brigitte M. Ronnett, Russell Vang, Jeffrey Lin, Tricia A. Murdock
American Journal of Surgical Pathology.2022; 46(12): 1611. CrossRef
Primary squamous cell carcinoma of the endometrium—Case report with cytological characteristics in direct and indirect endometrial samples
Sanda Rajhvajn, Ana Barišić, Lada Škopljanac‐Mačina, Danijela Jurič, Vesna Mahovlić
Cytopathology.2021; 32(6): 823. CrossRef
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Journal of Medical Case Reports.2019;[Epub] CrossRef
Primary squamous cell carcinoma of the endometrium in a woman of perimenopausal age
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Original Articles

The Expression of Pigment Epithelium-Derived Factor in Bladder Transitional Cell Carcinoma: Tae Jung Jang, Sung Woo Kim, Kyung Seop Lee; Korean J Pathol. 2012;46(3):261-265. Published online June 22, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.261

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Abstract PDF

Background

Pigment epithelium-derived factor (PEDF) is an anti-angiogenic factor. The purpose of this study is to examine the involvement of PEDF in the angiogenesis and biological behavior of bladder transitional cell carcinoma (TCC).

Methods

We examined the expression of PEDF in 99 bladder TCCs and ten non-neoplastic tissues, and evaluated microvessel density (MVD).

Results

The positive immunoreactivity for PEDF was seen in normal urothelium in 60% (6/10) and TCC in 13% (13/99). The PEDF expression had a significant correlation with MVD, i.e., a low MVD in 42% (5/12), a middle MVD in 11% (8/76) and a high MVD 0% (0/11) of tumors. The PEDF expression was not significantly correlated with the differentiation and invasion of TCC, but the degree of MVD was significantly higher in both high grade TCC and the pT2 tumors.

Conclusions

The degree of PEDF expression is significantly higher in normal bladder urothelium than bladder TCC; it is inversely correlated with the angiogenesis; and it is not related to the differentiation and progression of TCC. It can therefore be concluded that bladder TCC would initially occur if there is a lack of the PEDF expression.

Citations

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Association of pigment epithelium derived factor expression with cancer progression and prognosis: a meta-analysis study
Guo Cheng, Crystal Song
Discover Oncology.2021;[Epub] CrossRef
Level of mitoses in non-muscle invasive papillary urothelial carcinomas (pTa and pT1) at initial bladder biopsy is a simple and powerful predictor of clinical outcome: a multi-center study in South Korea
Ji Eun Kwon, Nam Hoon Cho, Yeong-Jin Choi, So Dug Lim, Yong Mee Cho, Sun Young Jun, Sanghui Park, Young A. Kim, Sung-Sun Kim, Mi Sun Choe, Jung-dong Lee, Dae Yong Kang, Jae Y. Ro, Hyun-Jung Kim
Diagnostic Pathology.2017;[Epub] CrossRef
Endogenous Gastric-Resident Mesenchymal Stem Cells Contribute to Formation of Cancer Stroma and Progression of Gastric Cancer
Eun-Kyung Kim, Hye-Jung Kim, Young-Il Yang, Jong Tae Kim, Min-Young Choi, Chang Soo Choi, Kwang-Hee Kim, Jeong-Han Lee, Won-Hee Jang, Soon-Ho Cheong
Korean Journal of Pathology.2013; 47(6): 507. CrossRef

Expression of Multidrug Resistance Protein 1 in Human Hepatocellular Carcinoma.: Yun Kyung Kang; Korean J Pathol. 2011;45(3):281-289.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.281

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Abstract PDF

BACKGROUND
Multidrug resistance protein 1 (MDR1) encoded by ATP-binding cassette, sub-family B (Mdr/Tap), member 1 (ABCB1) mediates cross-resistance to antineoplastic drugs, and its expression is related to tumor aggressiveness.
METHODS
MDR1 expression was investigated in 100 hepatocellular carcinomas (HCCs) by immunohistochemical staining. The epigenetic mechanisms underlying ABCB1 transcriptional regulation were investigated in cell lines.
RESULTS
MDR1 was normally localized in the bile canalicular surface of the hepatocytes. Among 100 HCCs, 45 showed canalicular/luminal (CL) staining similar to the normal pattern, another 45 displayed membranous/cytoplasmic (MC) overexpression, and the remaining 10 revealed loss of expression. MC pattern or null staining of HCCs correlated with a higher histological grade and had a poorer prognosis than HCCs with a CL pattern (p<0.05). They also tended to have a poor prognosis by multivariate survival analysis. The ABCB1 promoter was hypomethylated regardless of MDR1 expression or ABCB1 mRNA levels in 10 HCC cell lines. Histone deacetylase inhibitor treatment induced ABCB1 upregulation in 4 cell lines with low or moderate ABCB1 levels.
CONCLUSIONS
Our findings suggest that either an increase or a loss of MDR1 expression may contribute to the poor outcome of HCCs; histone deacetylation may be one of the epigenetic mechanisms directing the ABCB1 expression in HCCs.

Citations

Citations to this article as recorded by

Preferential expression of prostate specific membrane in CD34 labeled Neo-vasculature of Hepatocellular carcinoma: Prognostic and therapeutic potentials
Safaa MM Abd El Khalek, Mona QR Mohammed, Amira M Al Balakosy
Egyptian Journal of Pathology.2023; 43(1): 66. CrossRef

Prognostic Significance of Methylation Profiles in Urothelial Carcinomas of the Bladder.: Hee Jung Park, Eui Jin Lee, Sang Yun Ha, Ghee Young Kwon, Young Lyun Oh, Kyoung Mee Kim, Dae Shick Kim, Seongil Seo, Hyun Moo Lee, Han Yong Choi; Korean J Pathol. 2010;44(6):623-630.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.623

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Abstract PDF

BACKGROUND
Study on epigenetics of urothelial carcinomas has expanded and allowed better understanding of their correlation with clinicopathologic features. The aim of this study was to determine reliable predictive epigenetic markers for patients with urothelial carcinoma of urinary bladder.
METHODS
In 64 urothelial carcinomas of the urinary bladder, methylationspecific polymerase chain reaction with RAS association domain family 1A (RASSF1A), adenomatous polyposis coli (APC), death-associated protein-kinase (DAPK), runt-related transcription factor 3 (RUNX3), p14, p16 and MGMT was performed and correlated the results with p53 mutations, DNA ploidy, clinicopathologic parameters and recurrences.
RESULTS
Hypermethyation of RASSF1A, APC, DAPK, RUNX3, p14, p16 and MGMT promoters was observed in 35 (54.7%), 29 (45.3%), 18 (28.1%), 18 (28.1%), 9 (14.1%), 2 (3.1%), and 6 (9.4%) cases, respectively. Hypermethylation of RUNX3 and APC was significantly associated with high histologic grades and aneuploidy. Methylation of DAPK was significantly associated with muscle invasion. Methylation of DAPK and RUNX3 genes was significantly associated with recurrence. In survival analyses, methylation of RUNX3 gene and methylation-high (methylation at two or more loci) phenotype was significantly associated with poor recurrence-free survival.
CONCLUSIONS
Methylation of RUNX3 gene and methylation-high phenotype are significant indicator of recurrence.

Citations

Citations to this article as recorded by

DAPK Promoter Methylation and Bladder Cancer Risk: A Systematic Review and Meta-Analysis
Lihe Dai, Chong Ma, Zhensheng Zhang, Shuxiong Zeng, Anwei Liu, Shijie Tang, Qian Ren, Yinghao Sun, Chuanliang Xu, Shengtao Zhou
PLOS ONE.2016; 11(12): e0167228. CrossRef

Immunohistochemical Array for Clear Cell Type Mucoepidermoid Carcinoma.: Yeon Sook Kim, Sang Shin Lee, Ji Yong Song, Eun Cheol Kim, Suk Keun Lee; Korean J Pathol. 2010;44(3):284-294.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.284

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Abstract PDF

BACKGROUND
The protein expression profile of clear cell type mucoepidermoid carcinoma (MEC) is not well known.
METHODS
We examined a case of clear cell type MEC by immunohistochemical (IHC) array using 59 antibodies against oncoproteins, proliferation-related proteins, apoptosis-related proteins, growth factor-related proteins, angiogenesis-related proteins, and matrix proteins.
RESULTS
MEC tumor cells showed 40 to 60% more expression of BCL-2 and cyclin-dependent kinase 4 than normal gingival tissue, and 20-40% more expression of BCL-2-associated agonist of cell death, deleted in malignant brain tumors 1, E-cadherin, eIF5A, hypoxia-inducible factor, vimentin, and Wnt-1. Expression of other proteins, including p53, epidermal growth factor receptor, proliferating cell nuclear antigen, survivin, carcinoembryonic antigen, beta-catenin, poly-ADP ribose-polymerase, etc. were relatively weak in MEC tumor cells.
CONCLUSIONS
The IHC array for our MEC contained strong oncogenic signals involving Wnt-1/adenomatous polyposis coli, tumor necrosis factor a/signal transducer and activator of transcription 3/BCL-2, and pAKT pathways, signals that could result in the prolonged survival of clear tumor cells.

Citations

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Adolescent tongue base tumour with diagnostic histopathological dilemma
Mousam Maiti, Ajay Mallick, Debangshu Ghosh, Indranil Chakrabarti
BMJ Case Reports.2024; 17(8): e259570. CrossRef
A review: Immunological markers for malignant salivary gland tumors
P.C. Anila Namboodiripad
Journal of Oral Biology and Craniofacial Research.2014; 4(2): 127. CrossRef
DISPLACEMENT OF MAXILLARY LATERAL INCISOR CAUSED BY IDIOPATHIC GINGIVAL FIBROMATOSIS
Ji-Sook Jung, Ho-Won Park, Ju-Hyun Lee, Hyun-Woo Seo, Suk-Keun Lee
THE JOURNAL OF THE KOREAN ACADEMY OF PEDTATRIC DENTISTRY.2011; 38(3): 296. CrossRef

Microvessel and Lymphatic Vessel Density and VEGFR-3 Expression of Papillary Thyroid Carcinoma with Comparative Analysis of Clinicopathological Characteristics.: Harin Cheong, Hanna Kang, Hyung Kyung Kim, Ji Yoon Bae, Dong Eun Song, Min Sun Cho, Sun Hee Sung, Woon Sup Han, Heasoo Koo; Korean J Pathol. 2010;44(3):243-251.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.243

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Abstract PDF

BACKGROUND
This study was done to see if there were correlations between anatomic and molecular parameters such as microvessel density (MVD), lymphatic vessel density (LVD), and vascular endothelial growth factor receptor (VEGFR)-3 expression and various clinical parameters for papillary thyroid carcinomas of size > 1.0 cm (PTCs) and size < or = 1.0 cm (papillary thyroid microcarcinomas, PTMCs). PTMCs were divided into two subgroups (0-5 mm and 6-10 mm).
METHODS
We analyzed 197 thyroid carcinomas including 113 PTCs and 84 PTMCs. Tissue samples form 30 patients from each group matched for clinical characteristics were selected for immunostaining.
RESULTS
Although PTCs and PTMCs showed significant differences in clinical characteristics, they did not show significant difference in MVD, LVD, or VEGFR-3 expression. There was a significantly higher LVD in the PTMC subgroup with the larger tumors but no difference in clinical characteristics. LVD was higher in patients > 45 years old (more apparent in the PTC group) and LVD had suggestive correlations with multicentricity and extrathyroidal extension depending on analytic conditions.
CONCLUSIONS
Since LVD showed variable correlations with clinical variables for papillary carcinoma of the thyroid depending on analytic conditions, the individually planned treatments based on overall clinicopathological factors are advised.

Citations

Citations to this article as recorded by

Freeze-dried bovine amniotic membrane as a cell delivery scaffold in a porcine model of radiation-induced chronic wounds
Daemyung Oh, Daegu Son, Jinhee Kim, Sun-Young Kwon
Archives of Plastic Surgery.2021; 48(4): 448. CrossRef
Polydeoxyribonucleotide Improves Peripheral Tissue Oxygenation and Accelerates Angiogenesis in Diabetic Foot Ulcers
Seoyoung Kim, Junhyung Kim, Jaehoon Choi, Woonhyeok Jeong, Sunyoung Kwon
Archives of Plastic Surgery.2017; 44(06): 482. CrossRef

The Relationship between PTEN Tumor Suppressor Gene and Vascular Endothelial Growth Factor-Mediated Angiogenesis in Breast Cancer.: Jean Kyung Park, Min Jung Jung, Bong Kwon Chun, Bang Hur; Korean J Pathol. 2004;38(2):100-105.

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Abstract PDF: BACKGROUND
PTEN is a novel tumor suppressor gene located at chromosome 10q23.3. Loss of PTEN function has been implicated in the progression of several types of cancer. Angiogenesis is a critical factor in tumor growth and metastasis. We investigated PTEN expression in invasive breast cancers and described its role in the regulation of angiogenesis related to vascular endothelial growth factor (VEGF).
METHODS
Forty-five, surgically resected, formalin-fixed and paraffin embedded breast cancer tissue samples were analyzed for PTEN and VEGF expressions by immunohistochemistry and for microvessel density (MVD) by CD34 immunostaining.
RESULTS
Loss of PTEN expression was found in 35.6% (16/45) of the breast cancer tissues, all of which showed positive VEGF expression. Among 29 cases with normal PTEN expression, 15 (51.7%) were VEGF positive. MVD was significantly higher in tumors with a loss of PTEN expression than in those with normal PTEN expression.
CONCLUSION
A loss of PTEN expression might increase the VEGF-related angiogenesis in breast cancer. There was no correlation between PTEN expression and clinicopathologic parameters. Detection of the loss of PTEN expression may serve as a useful biologic marker for progression in invasive breast cancer.

VEGF Expression and Angiogenesis in Uterine Cervical Carcinomas.: Jin Sook Lee, Kang Suek Suh; Korean J Pathol. 1999;33(2):96-102.

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Abstract: Angiogenesis is a critical factor in the progression of solid tumors, including cervical cancers. The mechanisms responsible for angiogenesis in uterine cervical neoplasia are not well defined. To determine the relationship between angiogenesis and the expression of vascular endothelial growth factor (VEGF) in the cervical neoplasia, the author studied 63 cases of the cervical neoplasia diagnosed between the years 1993 to 1997 at Pusan National University Hospital. The expression of VEGF was semiquantitatively analyzed in paraffin sections by immunohistochemical method. Histologic sections immunostained for factor VIII-related antigen were evaluated for microvessel density. Increased expression of VEGF and microvessel counts was significantly correlated with depth of invasion. Increased microvessel counts were also significantly associated with increased VEGF expression. These results suggest that VEGF is an important angiogenic factor and associated with progression of the cervical neoplasia.

Clinical and Histopathologic Study of Eosinophilic Cellulitis.: Eun Kyung Kim, Chan Keum Park, Jung Dal Lee; Korean J Pathol. 1995;29(3):334-342.

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Abstract PDF: Eosinophilic cellulitis is a rare dermatosis originally described by Wells as "recurrent granulomatous dermatitis with eosinophilia", then called Wells' syndrome. The etiology is unknown, although a hypersensitivity mechanism is suspected. Flame figures are considered as a characteristic histologic feature of Wells' syndrome. To clarify the nature of eosinophilic cellulitis and its flame figures, the authors have reviewed five cases of eosinophilic cellulitis with its clinical and histopathologic findings. Cutaneous lesions were variable in appearance and was confused with angioedema, urticarial vasculitis, erydiema multiforme, morphea or granuloma annulare. Microscopically, early lesions (2-7 days) showed diffuse dermal eosinophilic infiltration with widespread degranulation, sometimes extended into the underlying muscle. Subepidermal bulla was present in one case. Subsequently, granulomatous features with characteristic "flame figures" became apparent (several months). Collagen alteration by eosinophilic granules resulted in flame figure formation and a granulomatous response. In two patients, there were possible relationships between drug and flare-ups of eosinophilic cellulitis, but the others, no contributory precipitating factors were found. We think that eosinophilic cellulitis represents a severe anaphylactic hypersensitivity reaction to various stimuli showing characteristic histopathology with recurrent episodes and frequent hypereosinophilia in the peripheral blood.

An Immunohistochemical Study of Angiogenesis in Tumor Emboli.: Jo Heon Kim, Chan Choi, Jae Hyuk Lee, Ji Shin Lee, Sung Sun Kim, Chang Woo Han, Sang Woo Juhng; Korean J Pathol. 2007;41(4):252-257.

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Abstract PDF: BACKGROUND
Angiogenesis, which is essential for tumor growth, is known to occur in the extravascular stroma. However, vascular structures were noted in intravascular tumor emboli in surgical specimens. This prompted our investigation of the frequency and morphology of angiogenesis in tumor emboli.
METHODS
Hematoxylin-eosin stained specimens were reviewed for tumor emboli, in 21 cases of stomach adenocarcinoma and 22 cases of colon adenocarcinoma. The cases were examined with immunohistochemistry using antibodies against epithelial antigen (cytokeratin), endothelial antigens (CD31, CD34), lymphatic endothelial antigen (D2-40), and proliferation-associated antigen (MIB1).
RESULTS
Endothelial cells were observed in 16 tumor emboli among four (19.1%) of the 21 cases of stomach adenocarcinoma and in 32 tumor emboli among four (18.2%) of the 22 cases of colon adenocarcinoma. The endothelial cells in the tumor emboli showed papillary ingrowth from the vessel wall, formation of vascular lumens, scattered distribution, or surface coating of the emboli. Some of the endothelial cells in the tumor emboli were D2-40-positive, and some were MIB1- positive.
CONCLUSIONS
These findings demonstrated that angiogenesis occurs in intravascular tumor emboli as well as in the extravascular stroma. Angiogenesis in the tumor emboli may reflect an active process and may facilitate tumor growth.

Case Report

Sebaceous Epithelioma: A report of 2 cases.: Youn Soo Lee, Mi Kyoung Jee, Seok Jin Gang, Byoung Kee Kim, Sun Moo Kim; Korean J Pathol. 1993;27(1):58-63.

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Abstract PDF: Sebaceous epithelioma is a relatively rare tumor, mostly occuring in the face or scalp. The histogenesis and clinical and pathological features of sebaceous epithelioma have not been clearly defined, and a few other diagnostic terms have been used so far instead of sebaceous epithelioma. Two cases of sebacous epitheliomas were presented. No recurrence or metastasis was observed in our cases, so sebaceous epithelioma is considered to be a benign tumor. A brief review of the literature, concerned about the biological behavior, histogenesis and pathological findings of the sebaceous epithelioma, was made.

Original Articles

Morphologic Difference of the Atrial Chambers and Determination of the Atrial Situs in the Normal and Congenitally Malformed Heart.: Eo Jin Kim, Jeong Wook Seo; Korean J Pathol. 2004;38(3):174-180.

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Abstract PDF: BACKGROUND
Identification of atrial situs is the initial step in any segmental analysis and classification of congenital heart malformations. To elucidate the differences for both atria of the normal and congenitally malformed heart, we performed morphological studies on the human heart with or without abnormal laterality syndrome.
METHODS
Five normally formed human hearts, five hearts with right isomerism and five hearts with left isomerism were used in this study. The postero-superior walls of the atrial chambers were examined.
RESULTS
Although the division line of the ventral and dorsal compartments was not as conspicuous as was seen in the right atrium of rat embryo previously studied, this division line existed as a well-developed terminal crest and vestigial structure of the antero-lateral extension of the terminal crest. These structures were noted in the right atrial chambers of normal human hearts and in the bilateral atrial chambers of right isomerism. However, they were totally absent in the bilateral atrial chambers in hearts with left isomerism.
CONCLUSIONS
Our study showed that the right atrial chamber in the normally developed human heart has vestigial components of division between the ventral and dorsal compartment, and hearts with right isomerism and left isomerism have differential development of the ventral and the dorsal compartment.

Microvessel Quantitation and Assessment of its Utility by CD34 Staining in Invasive Breast Carcinoma.: Hwa Sook Jeong, Ro Hyun Sung; Korean J Pathol. 1997;31(4):298-307.

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Abstract PDF: Tumor angiogenesis, the development of new blood vessels by tumor, is a widely observed phenomenon associated with the growth of human solid tumors. To investigate how tumor angiogenesis correlates with other prognostic features i.e. menopause status, tumor size, lymph node metastasis, mitosis, angioinvasion, estrogen receptor (ER), p53 protein expression, histologic grade and clinical stage, we counted microvessels by immunohistochemistry using antibody for CD34 antigen in 56 cases of invasive breast carcinoma (27 with and 29 without axillary lymph node metastases) and 20 cases of non-inflammatory benign breast lesion. CD34 antigen is expressed on the surface of hematopoietic progenitor cells and more sensitively expressed than factor VIII in vascular endothelial cells. Microvessel count (MVC) was performed at a single hot field of 200x magnification (0.74 mm2 per field). The results are summarized as follows; 1) The mean MVC of invasive carcinoma and benign breast lesion were 92.0+/-54.4 (range, 7-237) and 20.7+/-16.6 (range, 4-73), respectively (p<0.0001). 2) Although MVC had no correlation with all other prognostic factors i.e. menopause status, tumor size, lymph node metastasis, mitosis count, angioinvasion, ER, p53 protein expression, histologic grade, and clinical stage (p>0.05), MVC had a tendency to increase in tumors with axillary LN metastasis or without ER expression. 3) Without correlation with MVC, ER (+), angioinvasion (-) and higher histologic grade correlate to significantly higher mitosis count (p<0.0005). Also, angioinvasion correlate to a significantly higher histologic grade (p<0.05). In conclusion, angiogenesis is related to tumorigenesis, but MVC may not be related to other clinicopathologic factors.

Case Reports

Trichoadenoma: Report of a case.: Youn Soo Lee, Mi Kyung Lee, Seok Jin Gang, Byoung Kee Kim, Sun Moo Kim; Korean J Pathol. 1993;27(1):75-77.

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Abstract PDF: The clinical and pathological features of trichoadenoma are presented. Trichoadenoma is very rare, and as far as we know, no report on the trichoadenoma has been published in korea literature. We experienced a case of trichoadenoma occured in a 29 year-old male, who had a 0.9x0.7x0.4cm sized and slowly growing mass in the right buttock. The histopathological findings and histogenesis of trichoadenoma were discussed and a brief review of the literature was made.

Small Cell Osteosarcoma Similar to Ewing's Sarcoma in Histologic Findings and MIC2 Expression: A case report.: Yoon Mee Kim, Suk Woo Yang, Mee Yon Cho, Soon Won Hong, Byung Ho Choi; Korean J Pathol. 1999;33(3):204-209.

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Abstract PDF: Small cell osteosarcoma is a rare form of osteosarcoma and the histological differential diagnosis from other small round cell tumors (SRCTs) is difficult. The immunohistochemical stain for MIC2 has been considered an useful diagnostic marker for Ewing's sarcoma and primitive neuroectodermal tumors but recently, other SRCTs such as malignant lymphoma and embryonal rhabdomyosarcoma also showed positive reaction. Therefore, the usefulness of MIC2 must still be proven. We experienced a case of small cell osteosarcoma of the mandible in a 25-year-old man. Histologically, the tumor consisted of small round cells that resembled those of Ewing's sarcoma. Immunohistochemically, the tumor cells expressed diffuse strong positive reaction for MIC2 gene products. However, the scanty foci of lacy osteoid material between the tumor cells seemed to be diagnostic of osteosarcoma. The histologic and immunohistochemical findings of this case suggest close relationship between small cell osteosarcoma and Ewing's sarcoma.

Clear Cell Sarcoma of the Kidney: A case report.: Soon Ae Oak, Bang Hur, Man Ha Huh; Korean J Pathol. 1993;27(1):81-84.

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Abstract PDF: Clear Cell Sarcoma of the Kidney(CCSK) is a rare malignant childhood tumor which is distinguished from Wilms tumor by its pathologic features, clinical presentation and frequent occurrence of metastasis to bone. We report a case of CCSK from a 2 year-old girl in the right kidney, followed by metastasis to thoracic vertebrae and left temporal lobe. Histogenesis of this tumor is controversial, although some studies suggest primitive mesenchymal origin. This case was studied with the aids of immunohistochemistry and electron microscopy in an effort to verify the histogenesis of the tumor. Vimentin was reactive in tumor cell, but cytokeratin, GFAP, S-100 protein and desmin were not stained, which confirmed the previous reports by others. Ultrastructural observation of the tumor cells showed neither features of epithelial cell nor differentiated mesenchymal cells.

Original Articles

The Significance of the Expression of p53, E-cadherin, nm23, CD44, and Tumor Angiogenesis in Colorectal Adenocarcinoma.: Sung Suk Paeng, Hee Jin Chang, Jung Il Suh; Korean J Pathol. 1997;31(4):314-325.

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Abstract PDF: Many oncogenes and tumor supressor genes have been identified and studied in colorectal carcinoma. Among them, p53 is a tumor supressor gene and its mutation is frequently noted in human tumors. E-cadherin is a cell adhesion molecule and associated with tumor differentiation. CD44 is a cell surface glycoprotein that plays a role in cell migration and metastasis. nm23 is a gene known to lower metastatic potential of tumors and has been proposed to be a metastasis supressor gene. Tumor angiogenesis is required for the expansion of the primary tumor and metastasis and its degree is related to the potential of malignancy. We studied the expression of p53, E-cadherin, nm23, CD44 and tumor angiogenesis in 36 cases of colorectal adenocarcinomas. They were compared with previously known prognostic factors such as the stage, tumor size, depth of invasion, differentiation, presence of lymphatic or venous invasion, the lymph node and distant metastasis. The results were as follows. 1) The expression of p53 was not significantly associated with any prognostic factors. 2) The expression of E-cadherin was significantly associated with tumor differentiation. In the well differentiated adenocarcinomas, its expression was higher than in the poorly differentiated adenocarcinoma. 3) The expression of nm23 was also significantly associated with tumor differentiation. In carcinoma with lymph node metastasis, the expression of nm23 was reduced, but statistically it was not significant. 4) The expression of CD44 was higher in tumors with lymph node metastasis than in tumors without lymph node metastasis, but it was not statistically significant. 5) The degree of microvessel density was significantly associated with lymphatic invasion. According to the above results, the expression of E-cadherin and nm23 are related to the differentiation of the tumor and tumor angiogenesis is related to the lymphatic invasion of the colorectal adenocarcinoma.

The Apoptotic Molecular Changes of Cellular Injury in Mouse Testis Induced by Endocrine Disrupting Chemicals.: Eun Hui Wang, Kweon Heang Lee, Ki Hwa Yang, Jinsuk Lee, Eun Sun Jung, Chang Suk Kang, Yeong Jin Choi; Korean J Pathol. 2004;38(4):228-237.

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Abstract PDF: BACKGROUND
Spermatogenesis is regulated by various cellular reactions, and especially cell proliferation and apoptosis.
METHODS
We investigated the morphological changes and the apoptotic molecular changes in mouse testis induced by the endocrine disrupting chemicals. ICR mice were treated with bisphenol A (BPA), 2-bromopropane (2-BP) and diethylstilbesterol (DES). Histological examination and immunohistochemical staining, TUNNEL staining and RNAse protection assay were conducted.
RESULTS
Testes treated with BPA showed normal spermatogenesis and the proliferation activity, and the density of the cells was similar with those in the control. 2-BP and DES groups, which showed a decrease of germ cells near the basal layer and degenerative changes. The proliferative activity identified by PCNA staining was significantly decreased in the 2-BP and DES groups (p<0.05). The apoptosis was significantly increased in the 2-BP group however, a significant decrease was noted in the BPA group (p<0.05). Among apoptosis-related molecules, the expression of Fas, Fas ligand, TRAIL, TNFp55 and caspase 1, 3, 6 and 8 were changed according to the change of the degree of apoptosis in all groups.
CONCLUSIONS
Endocrine disrupting chemicals induced cellular injury in mouse testis through the changes of proliferative activity and apoptosis which was regulated by a number of apoptosis-related molecules. This probably results in the abnormality of spermatogenesis in mouse testis.

Correlation of Tumor Angiogenesis and nm23-H1 Expression with Lymph Node Metastasis in Proper Muscle Gastric Cancer.: Eun Sook Nam, Gu Kang, Hyung Sik Shin, Young Eui Park; Korean J Pathol. 1997;31(5):410-416.

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Abstract PDF: We studied clinicopathologic features of 44 cases of PM (proper muscle) gastric cancer, correlated the lymph node metastasis and found the result of immunohistochemical staining for tumor angiogenesis using antibodies to Factor VIII-related antigen and nm23-H1, known as meatastasis inhibitory substance. The results were as follows: 1) The average age of these 44 cases of PM gastric cancer was 55.1 years old (range 35-81). The ratio of male to female was 2.2 : 1. The tumor was located at the antrum of stomach in 72.7% of the cases. The average size of the tumor was 4.1 cm (range 0.6-9). The gross features were comprised of Borrmann type I (6.8%), II (29.6%), III (56.8%), IV (6.8%), respectively. The microscopic type was a diffuse type in 70.5% and an intestinal type in 29.5%. There were lymph node metastasis in 25 of the 44 cases (56.8%). 2) The microvessel count was higher in the lymph node positive group (average 69.3) than in the lymph node negative group (average 45.6) (P=0.004). There was a higher microvessel density in diffuse type, over 4 cm of tumor size, proximally located tumor, older than 50 years, Borrmann type II and IV, but there was no statistically significant correlation. 3) The more decreased expression of nm23-H1 was found in the lymph node positive group (56.0%) than in the lymph node negative group (31.6%), but showed no statistical significance (P=0.0142). There was no significant correlation between the expression of nm23-H1 and the other clinicopathologic factors. We suggest that the microvessel count of the tumor angiogenesis may be a prognostic factor for predicting lymph node metastasis and also help to determine the therapeutic modalities of PM gastric cancer.

Expression of bcl-2 Protein in Colorectal Adenoma and Adenocarcinoma and its Relationship with p53 and Apoptosis.: Ae Ree Kim, Seong Jin Cho, Nam Hee Won, Yang Seok Chae; Korean J Pathol. 1997;31(5):417-426.

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Abstract PDF: Either increased cellular proliferation or decreased death might result in an expansion of their numbers in the oncogenic process. Cellular apoptosis represents an autonomous suicide pathway that helps to restrict the cell number. However bcl-2 and mutant p53 inhibit programmed cell death. To determine whether the bcl-2 gene is activated during colorectal tumorigenesis and whether it has any relationship with p53 and apoptosis, we studied the expression of bcl-2 and p53 in the normal colonic mucosa, in the adenomatous polyps and in the adenocarcinomas using the immunohistochemical method. Also we evaluated the status of apoptosis using the in situ end labeling method. The bcl-2 immunoreactivity was restricted to the basal epithelial cells of all normal colonic mucosa and they were expressed in all adenomas and 86% of adenocarcinomas, especially in the superficial lesion of some tumors. Mutations of p53 were not found in the normal colonic mucosa, but they were present in dysplastic cells of adenomas (52%) and in cancer cells of the adenocarcinomas (47%). Apoptosis was confined to the tips of the normal colonic mucosa. It was more easily detected in the p53-positive adenomas than in the p53-negative adenomas (p=0.010). In the adenocarcinomas, the findings of apoptotic process are not related with p53 mutation (p=0.3) and bcl-2 expression (p=0.187). p53 and bcl-2 are probably one step of several apoptotic processes in the adenocarcinomas.

Expression of CDK 4, Connexin 32, and PCNA in N-diethylnitrosamine-Induced Lesions of Rat Liver.: Bang Hur, Hung Jun Kim; Korean J Pathol. 1999;33(5):309-318.

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Abstract PDF: Cellular altered foci (CAF), hyperplastic nodules (HN) including regenerating and adenomatous nodules, and hepatocellular carcinomas (HCC) were induced in Sprague-Dawley rat liver by prolonged administration of N-diethylnitrosamine (DEN, 200 ppm). Immunohistochemical expression of connexin 32 (Cx 32), cyclin-dependent kinase 4 (CDK 4), and proliferating cell nuclear antigen (PCNA) was assessed for the evaluation of preneoplastic potential of CAF. Regardless the duration of DEN administration, basophilic cell foci were the most frequently observed lesion in both CAF and cellular expanding hyperplastic nodules. Eosinophilic cell foci, however, were concomitantly increased with adenomatous nodules in later experimental groups. Cx 32 showed perimembranous spot-like expression. Its number was 7.25 2.10 per cell in normal hepatocytes. CAF and adenomatous nodules showed markedly decreased Cx 32 spots. Moreover, its reduction was more prominent in HCC. PCNA-labelled hepatocytes were scattered in the most CAF, showing no significant difference between each CAF. PCNA labelling index (LI) in adenomatous nodule and HCC was markedly increased. CDK 4 was localized in the cytoplasm and/or nucleus of hepatocytes. Eosinophilic cell foci revealed more nuclear expression of CDK 4 than other types of CAF, of which expression incidence was comparable to that of adenomatous nodule. Nuclear CDK 4 expression in HN and HCC was increased, although significant difference between regenerating nodule and adenomatous nodule was not seen. In conclusion, the incidence of CDK 4 was concomitantly increased with PCNA LI, however, reciprocally decreased with Cx 32 in accordance with the advance of DEN-induced HCC in rat. Phenotypically altered foci manifested as CAF are early valuable preneoplastic marker lesion for evaluation. In addition, basophilic cell foci can be considered a discernible marker of cellular expansion within nodules. However, eosinophilic cell foci might be an indeterminate marker for the advance of DEN-induced HCC in rat.

Human Papillomavirus Type 16, 18, and 33 Infection in Adenocarcinoma of the Uterine Cervix: Analysis of the p53 Gene Mutation and the Clincopathologic Correlation.: Kwang Sun Suh, Seong Jun Cho, Sun Young Na, Heung Tae Noh, Sang Ryun Nam; Korean J Pathol. 2004;38(5):295-300.

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Abstract PDF: BACKGROUND
Current evidence implicates specific types of the human papillomavirus (HPV) are involved in the development of cervical cancer. In HPV-negative cervical carcinomas, p53 mutation is thought to be a mechanism of oncogenesis. The purpose of this study was to evaluate the prevalence of p53 mutations in cervical adenocarcinomas and to investigate their correlation with HPV status and clinicopathologic parameters.
METHODS
A series of 38 primary cervical adenocarcinomas was analyzed for both HPV infection and p53 mutations. The HPV 16, 18, and 33 status was investigated by PCR amplification. The point mutations of the p53 gene were detected by the PCR-SSCP technique.
RESULTS
The prevalence of HPV 16, 18, or 33 infection was 73.7% (28/38). HPV 16 was present in 12 cases, HPV 18 was present in 15 cases, and HPV 33 was positive in one case. There was only one case that was positive for 18 as well as a p53 mutation in exon 6.
CONCLUSIONS
Our results indicate that HPV 18 infection was more common in cervical adenocarcinomas than HPV 16 infection. Mutant p53 was rarely found in cervical adenocarcinomas regardless of the type of HPV infection. There was no correlation between HPV infection and clinical stage or pathologic type of tumor.

Expression Pattern of Smad Proteins in Diffuse Large B-cell Lymphomas.: Jai Hyang Go; Korean J Pathol. 2004;38(5):301-305.

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Abstract PDF: BACKGROUND
Smad proteins mediate the cellular signaling from members of transforming growth factor-beta family (TGF-beta s). Smads 2 and 3 transmit signals from TGF-beta and activin, and Smads 1, 5, and 8 transmit signals from the bone morphogenetic protein. Smad4 is known to be a common mediator of both pathways, yet little is known about the expression pattern of Smad proteins in normal lymphoid tissue and malignant lymphoma.
METHODS
Immunohistochemistry was performed for Smad3 and Smad4 on the paraffin-embedded tissue sections from 32 cases of diffuse large B-cell lymphomas.
RESULTS
In reactive lymphoid tissue, nearly all cells of the germinal centers were positive for Smad3 and more than 50% of paracortical cells were positive for Smad3. For Smad4 immunostaining, nearly all cells of the germinal centers showed diffuse cytoplasmic staining, and most of them revealed nuclear positivity as well. Most of the cells in the paracortex regions were positive for Smad4. For the malignant lymphomas, all the cases were positive for Smad3, but 26 cases were positive for Smad4 and 6 cases (19%) were negative for Smad4.
CONCLUSIONS
These results suggest that TGF-beta-specific Smads may be actively involved for signal transduction in lymphoid organs, and the TGF-beta signaling pathway through Smads is operative in malignant lymphoma. The loss of Smad4 expression might be associated with development of some diffuse large B-cell lymphomas.

Case Report

Achondrogenesis Type 2: An autopsy case.: Joon Mee Kim, Young Chae Chu, Soo Kee Min, Hee Jeung Cha, Je Geun Chi; Korean J Pathol. 1997;31(5):482-488.

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Abstract PDF: Achondrogenesis type 2 is a lethal form of congenital skeletal dysplasia characterized by severe short-limbed dwarfism, decreased vertebral ossification and normal ossification of the skull. We report an autopsy case of achondrogenesis type 2 in a female fetus terminated at 29 weeks of gestation. External morphology revealed a relatively large head, short upper and lower extremities, short neck, and distended abdomen. The x-ray finding showed normal calvarial ossification, hypoplastic ilium and unossified ischium, and metaphyseal flares of the femur and tibia. Histologically, chondrocytes were large and irregular with increased vascularity.

Original Articles

Body Stalk Anomaly: Analysis of 10 Autopsy Cases.: Seung Sook Lee, Je G Chi; Korean J Pathol. 1993;27(3):235-242.

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Abstract PDF: Body stalk anomaly represents an extreme maldevelopment of embryonic body folding and is characterized by absence of the umbilicus and umbilical cord. The failure of complete obliteration of the extraembryonic coelom is responsible for the absence of the umbilical cord formation and the wide-based insertio of the amnioperitoneal membrane onto the placental chorionic plate. We have analyzed 10 autopsy cases of various midline anomalies of the body that could best be classified into body stalk anomaly. All cases were either stillborns or dead immediately after birth. The pregnancy was interrupted due to this anomaly in 6 cases, and their gestational ages varied from 17 weeks to 37 weeks. The affected fetuses were characterized bt absent or vestigial umbilical cord, and ruptured amnion with direct amnioperitoneal connection without the mediation of the umbilical cord. Exomphalos with abdominal wall defect and serve scoliosis were characteristic components of this anomaly, that provided important clues in differentiating other similar anomalies. Other associated anomalies included neural tube defect, intestinal atresia, genitourinary and skeletal defects, pulmonary hypoplasia, single umbilical artery and narrow-spaced chest and abdomen, etc. These findings strongly suggest that anomaly of body stalk represents mechanical teratogenesis due to early amnion repture and subsequent effect, and should be categorized into amniotic band disruption syndrome.

A Study on the Expression of p53 and nm23 Protein in the Colorectal Adenoma and Carcinoma.: Jin Hee Sohn, Eun Ha Jung, Hye Rim Park, Young Eui Park; Korean J Pathol. 1997;31(6):508-516.

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Abstract PDF: The expression of the nuclear phosphoprotein p53, a product of tumor suppressor gene, has been noted in a number of human tumors as a tumor suppressor. nm23 is a gene associated with low tumor metastatic potential and has been proposed to be a metastasis suppressor gene. To assess the role of p53 and nm23 expression in colorectal tumorigenesis and the association with clinicopathological parameters, an immunohistochemical study for mutant p53 and nm23 was done using mouse monoclonal antibodies in 43 colorectal carcinomas, 55 tubular adenomas and corresponding normal mucosa. In the tubular adenomas, p53 expression was significantly correlated with the degree of atypism(p<0.05) but not with other variables as well as with nm23. In the colorectal carcinoma, there were evidence of some correlation between metastasis, laterality and p53; laterality, depth of invasion and nm23 expression, but without statistical significance. Other clinicopathologic features were not significantly correlated. In the aspect of 'adenoma-carcinoma sequence', normal mucosa was totally negative for both p53 and nm23, and they were increasingly expressed through tubular adenoma to carcinoma with statistical significance(p<0.05). Therefore, it is suggested that both p53 and nm23 expressions occur in and around the time of transition to carcinoma from adenoma but are not significantly associated with the infiltrative behavior and metastasis.

Diffuse Large B Cell Lymphoma Shows Distinct Methylation Profiles of the Tumor Suppressor Genes among the Non-Hodgkin's Lymphomas.: Sun Och Yoon, Young A Kim, Yoon Kyung Jeon, Ji Eun Kim, Gyeong Hoon Kang, Chul Woo Kim; Korean J Pathol. 2008;42(1):16-20.

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Abstract PDF: BACKGROUND
Aberrant methylation of CpG islands in promoter regions is one of the major mechanisms for silencing of tumor suppressor genes in various types of human cancers including non-Hodgkin's lymphomas (NHL). In this study, we investigated the aberrant promoter methylation status of known or suspected tumor suppressor genes in NHLs and compared the methylation profiles between B-cell and T/NK-cell NHLs.
METHODS
54 cases of B-cell NHLs and 16 cases of T/NK-cell NHLs were examined for the methylation status of eight genes using methylation specific PCR.
RESULTS
CpG islands methylation was variously found in eight genes as follows; DAPK (71%), MT1G (70%), p16 (53%), CDH1 (53%), THBS1 (56%), MGMT (27.1%), COX2 (13%), and RUNX3 (11.4%). In six cases (8 %), methylation was not observed in any of these genes. Overall methylation index of B-cell NHLs (0.48) was significantly higher than that of T/NK-cell NHLs (0.32). Of eight genes tested, THBS1 and CDH1 methylations were much more prominent in diffuse large B-cell lymphomas than in T/NK-cell NHLs or other B-cell NHLs.
CONCLUSION
This study suggests that aberrant CpG island methylation is a frequent event in NHLs, and diffuse large B-cell lymphomas show overlapping but distinct methylation profiles.

Correlation between Tumor Angiogenesis (Microvessel Density), Metastasis and Tumor Cell Proliferation in Colorectal Carcinomas.: Young Chae Chu, Joon Mee Kim; Korean J Pathol. 1997;31(6):517-526.

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Abstract PDF: Tumor angiogenesis has been shown to be associated with metastatic potentials in breast, lung and prostatic carcinomas. The relation between tumor angiogenesis and metastatic potentials in colorectal cancer has not been established to date. We analysed 66 selected patients with colorectal carcinomas (37 with and 29 without nodal metastases) for the microvessel density, tumor proliferation activity, and the clinicopathologic parameters including size, stage, histologic grade, growth pattern, presence of angioinvasion, perineural invasion and lymph node metastasis. For evaluation of microvessel density and tumor proliferative activity, the primary tumors were immunohistochemically stained for CD31 and PCNA. The mean microvessel counts (MVC) per 200X field were 99.27+/-23.28 and 131.35+/-31.48 in node-negative and node-positive patients, respectively. The PCNA index was 39.41+/-5.63% and 56.60+/-7.09% in node-negative and node-positive patients, respectively. MVC and PCNA index were higher in tumors with nodal metastasis (p=0.002, p<0.001), and also correlated each other (sr=0.33, p=0.007). Higher microvessel counts were seen in tumors with advanced stage (p=0.016). Tumor proliferation activity assessed by PCNA immunostaining was significantly higher in tumors with advanced stage, perineural invasion, angioinvasion, poor differentiation and larger size. From these results, MVC and PCNA index in colorectal carcinomas are assumed to be valuable prognostic parameters. Thus assessment of tumor angiogenesis and tumor cell proliferation in colorectal carcinomas may be helpful for the patients in need of aggressive therapy.

Case Report

Hamartoma Arising in the Urinary Bladder: A case report.: Young Bae Kim, Tae Sook Hwang, Byung Gon Park, Jin Sook Jeong, Sook Hee Hong; Korean J Pathol. 1993;27(3):283-286.

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Abstract PDF: Hamartoma of the bladder is quite a rare entity which is composed of a disorderly admixture of mature cellular elements normally present in the urinary bladder. There is a great controversy regarding the pathogenesis of this lesion. Whether it is a true hamartomatous lesion or metaplastic lesion developed secondary to the inflammatory process. Similar or identical lesions has often been given by other names such as florid examples of cystitis glandularis. We prefer to cell florid examples of cystitis glandularis rather than hamartoma when it was occurred in an old age higher then 50th decade. Here we report a case of hamartoma of the urinary bladder in 44 years old man. Cystoscopic examination revealed a papillary polypoid mass which was attached to the fundus of bladder by long stalk. The mass measured 1.5 cm in greatest diameter. It was composed of epithelial nests resembling von Brunn's nest, cystitis glandularis or cystitis cystica dispersed in a stroma rich in smooth muscle and fibrous tissue.

Original Articles

Characterization of Principal Component Cell of DMBA induced Rat Malignant Fibrous Histiocytoma With Cell Culture and Cloning.: Myeng Sun Park, Hae Jin Jeong, Man Ha Huh; Korean J Pathol. 1997;31(6):574-585.

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Abstract PDF: This experiment was performed to elucidate the cytologic origin of chemically induced MFH in Wistar rats. The tumor was produced by injections of DMBA(9,10-dimethyl-1,2-benzanthracene). With the produced MFH, cell culture and cloning were performed, followed by establishment of a cell strain, which was investigated by immunohistochemical and electron microscopic studies. The results were as follows. A) By immunohistochemistry of the tumor tissue, fibroblastic cells were positive for MEP-1(specific antibody for fibroblastlike cell of MFH, Takeya, 1993) and Anti-hPH(beta)(Anti-prolyl 4-hydroxylase beta), but negative for TRPM-3 and F4/80. Histiocytelike cells were positive for TRPM-3 and F4/80, but negative for MEP-1 and Anti-hPH(beta). In immunoelectron microscopy, normal spleen macrophage showed linear reactivity in cell membrane for TRPM-3, whereas histiocytelike cells of the tumor disclosed negative reaction. B) At 5 weeks of the primary tumor cell culture, the cells exhibited typical storiform pattern of MFH. C) The established cell strain revealed immunoreactivity for MEP-1 and Anti-hPH(beta), but negative for TRPM-3. The cloned tumor cells showed morphologic characteristics of undifferentiated fibroblastic cell. Latex particle (0.80 micrometer size) phagocytosis was negative in the cloned cell strain. The results of the current study support the concept that principal component cells of MFH is of fibroblastic cell origin.

Correlation between Tumor Angiogenesis and Metastasis in Invasive Breast Carcinoma.: Nam Hoon Kim, Moon Hyang Park; Korean J Pathol. 1995;29(6):740-745.

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Abstract PDF: Tumor angiogenesis(TA) refers to the growth of new vessels toward and within a tumor. TA is necessary both at the beginning and at the end of the metastatic cascade of events. Recently, experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis. To investigate how tumor angiogenesis correlates with metastases in breast carcinoma, the microvessels were counted (per 200 / field) in the most active areas of neovas-cularization by two investigators. The microvessels within breast carcinoma were highlighted by in imunohistochemical staining for factor VIII-related antigen. Microvessel count(MVC) in node-positive carcinoma(59.66=35) was significantly higher than in node-negative carcinoma(44.76=17)(p=0.009). MVC was also statistically correlated with tumor size and stage, but not with histologic grading, DNA ploidy, or hormonal receptors(estro-gen and progesterone). MVC in invasive breast carcinoma may be one of many prognostic predictors of node-positive breast carcinoma. Assessment of tumor angiogenesis may therefore be valuable in selecting patients with early breast carcinoma for aggressive therapy.

Microvessel Density and Expressions of bcl-2, p53, and Vascular Endothelial Growth Factor in Endometrial Carcinoma.: Soon Young Kim, Hae Jin Jeong, Myeng Sun Park, Bang Hur; Korean J Pathol. 2001;35(5):401-407.

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Abstract PDF: BACKGROUND
Recent studies have shown that oncogenes and tumor suppressor genes are involved in tumorigenesis and tumor progression. The inverse role of bcl-2 and p53 in endometrial carcinomas has been debated. Moreover, their roles in angiogenesis as well as the interrelationship between prognostic clinico-pathological factors and angiogenesis have not been elucidated in endometrial carcinomas.
METHODS
The expression rates of bcl-2, p53 and vascular endothelial growth factor (VEGF) in thirty-eight cases of surgically removed endometrial carcinomas were investigated using an avidin-biotin complex method of immunohistochemistry. CD34 immunostain for microvessel density (MVD) was also performed.
RESULTS
The expression rate of bcl-2 was higher in the endometrioid type carcinoma (43.8%) than in the non-endometriod type carcinoma (16.7%). There was a significantly increased bcl-2 expression in grade I compared to grades II and III (P<0.05). The p53 expression rate was significantly higher in the non-endometriod type carcinoma than in the endometrioid type carcinoma (P<0.05).The VEGF expression rate was higher in the non-endometriod type carcinoma (83.3%) than in the endometrioid carcinoma (28.1%). Differences of MVD according to stages, histological types, grades and bcl-2, p53 and VEGF expressions were not noted.
CONCLUSIONS
The expression rate of bcl-2 increases in the low grade endometrial carcinoma more than in the high grade one, so it may be suggested that bcl-2 expression could be used for an ancillary prognosticator. However, p53 and VEGF expressions and microvessel density may not have any prognostic value.

PTEN and p53 Mutations in Endometrial Carcinomas.: Jae Sung Choi, Kwang Sun Suh, Heung Tae Noh, Yun Ee Rhee, Sun Young Na, Hye Kyung Lee; Korean J Pathol. 2005;39(1):1-8.

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Abstract PDF: BACKGROUND
Endometrial carcinomas are pathogenetically classified into two major types; endometrioid carcinoma (EC) and serous carcinoma (SC). The most frequently altered gene in EC is the PTEN tumor suppressor gene (TSG). SC is usually associated with mutations in the p53 TSG.
METHODS
To further determine the role of PTEN and p53 mutation in endometrial carcinogenesis, the analysis of 33 endometrial carcinomas, including 28 ECs and 5 SCs, for loss of heterozygosity (LOH) on 10q23 and for mutation in all 9 coding exons of PTEN and the 5-8 exons of p53, using SSCP-PCR methods was carried out.
RESULTS
LOH was detected in at least one marker in 12 (54.5%) of 22 ECs, but in only one (20.0%) of 5 SCs. Somatic PTEN mutations were detected in 10 (35.7%) of 28 ECs. PTEN was altered in 67.9% of ECs and in 20.0% of SCs, including those with 10q23 LOH. No PTEN mutations were found among the SCs. Somatic p53 mutations were detected in 2 (7.1%) of 28 ECs and 3 (60.0%) of 5 SCs.
CONCLUSIONS
PTEN gene alterations contribute to the pathogenesis of an endometrioid subtype of endometrial carcinoma, but not to the serous type. In contrast, p53 plays an important role in the pathogenesis of SCs.

Case Report

Epidermoid Cyst of the Ovary: Two case reports.: Hyuni Cho, Yu Hoon Kim, Eun Suk Nam, Insun Kim; Korean J Pathol. 1995;29(6):811-814.

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Abstract PDF: Two cases of epidertnoid cyst of the ovary are added to the ten reported in the literature. This rare lesion is usually an incidental finding. Its main interest is in its histogenesis, which includes metaplasia of the coelomic surface epithelium, monophyletic development of teratoma, and metaplasia of the rete ovarii. We investigated two cases of epidertnoid cyst. Histologic examination of the cysts showed a thin lining of mature keratinizing squamous epithelium rectum: unaccompanied by skin appendages or other teratomatous elements.

Original Articles

Tumor Angiogenesis and Cathepsin-D Expression in Invasive Ductal Carcinoma of the Breast.: Young Gyung Bae, Dae Hong Suh, Dong Sug Kim, Soo Jung Lee; Korean J Pathol. 1997;31(8):735-744.

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Abstract PDF: This study was conducted to assess the prognostic value of tumor angiogenesis and Cathepsin-D in breast carcinoma, by correlating them with other clinicopathologic prognostic factors. In order to estimate microvessels within the tumor, an immunohistochemical method using monoclonal antibodies for factor VIII-related antigens (DAKO-vWf, F8/86) was used, and they were counted (perx200 field) in the most active areas of neovascularization. For the expression of Cathepsin-D, an immunohistochemical method using monoclonal antibodies (Novocastra, NCL-CDm) was performed. The microvessel count ranged from 8 to 346 per x200 field and the mean (+/-SD) was 72.46+/-54.96. The microvessel count was correlated with the estrogen receptor status, and it was also correlated with the tumor size when it was graded into four groups (1-33, 34-67, 68-100, >100), but was not correlated with other clinicopathologic parameters. Cathepsin-D was expressed in 40% (46/115) of the cases, but it was statistically correlated with the tumor size only. In conclusion, the expression of Cathepsin D and the degree of angiogenesis in breast cancer showed a correlation with the tumor size only. Therefore, they do not appear to be good prognostic parameters, according to the present study.

Immunohistochemical Study of E-cadherin Expression in Gastric Adenocarcinomas.: Jee Yeon Kim, Mee Young Sol, Sun Kyung Lee; Korean J Pathol. 1997;31(8):745-753.

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Abstract PDF: E-cadherin (ECD) is a Ca++ -dependent adhesion molecule which plays a major role in the maintenance of intercellular adhesion in epithelial tissues. The expression pattern of ECD in 77 surgically resected gastric adenocarcinomas was examined by immunohistochemistry, using a rat monoclonal antibody raised against murine E-cadherin (DECAM-1). ECD was strongly expressed uniformly at cell to cell borders in normal gastric epithelium without exception. But, various staining patterns were observed in the cancer tissues. The frequency of tumors with preserved ECD expression (Pre-type) and reduced ECD expression (Rd-type) was 44% and 56%, respectively. Using Lauren's classification, the high frequency of the Pre-type expression in adenocarcinoma of the intestinal type was significantly higher than that in adenocarcinoma of the diffuse type (p<0.05). But, no significant correlation between the ECD expression and the gross type, invasion depth, growth pattern or metastasis was observed. These results suggest that ECD might play a key role in the morphogenesis of gastric adenocarcinoma.

Sequential Ultrastructural Change of Chorionic Villi in Human Placenta by Gestational Period.: Tae Dong Park, Tae Jung Kwon, Je G Chi; Korean J Pathol. 1993;27(5):468-484.

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Abstract PDF: A study was performed to observe the sequential morphological change of the human placental barrier by means of light microscopy, immunohistochemistry, scanning electron microscopy and transmission electron microscopy. The examined placentas ranged in age from 4 weeks gestation to the full-term(40 weeks). Sixty seven placental specimens were obtained immediately after delivery. With the progression of gestation, the microvilli on the surface of syncytinum tended to be fewer, shorter and blunter. The syncytiotrophoblasts were getting thinner with formation of vasculo-syncytial membrane. The cytotrophoblasts formed a continuous layer which progressively disappeared but still present in the mature villi. In view of presence of intermediate cells and remnant of desmosomes, the cytotrophoblasts appeared to form the syncytiotrophoblasts. In early pregnancy, capillary formation took place by the aggregation and differentiation of the proliferation and aggregation of endothelial cells and pericytes. Myofibroblasts in villous stroma were examined by desmin immunohistochemical staining, and detected from 19 weeks to the full-term. During last period of pregancy definitive smooth muscle cells could be demonstrated, suggesting that the presence of myofibroblasts or smooth muscle cells are closely related to the placental maturity. Scanning electron microscopy of the early placenta showed numerous syncytial sprouts representing stages in the formation of new villi, but in the late period of gestation syncytial sprouts were diminished. It is concluded that the syncytiotrophoblast is originated from the cytotrophoblast in early pregnancy as the placental barrier is formulated. Moreover, myofibroblasts and smooth muscle cells in villous stroma play important role in placental maturation.

Tumor Angiogenesis and Stage in Ovarian Carcinoma.: Eun Sook Chang, Hyun Chang Joo, Tae Sung Lee; Korean J Pathol. 1999;33(8):596-602.

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Abstract PDF: Tumor angiogenesis has been found to have prognostic significance in many tumor types for predicting an increased risk of metastasis. We assessed tumor vascularity in 28 cases of borderline malignancy and 71 cases of carcinoma of the ovary which had been resected and diagnosed, using the highly specific endothelial cell marker CD34. The numbers of microvessels were counted in 200 magnification in three highly vascularised areas. The numbers of microvessels in carcinomas were higher than that in the borderline malignancy of serous and mucinous tumors. The number of microvessels of mucinous carcinomas was significantly higher than that of serous carcinomas. There were neither significant differences in the number of microvessels according to histological tumor types (p=0.075) nor significant differences in the number of microvessels according to FIGO stages (p=0.072). But in serous carcinomas, the number of microvessels was higher in the FIGO III-IV stage than in the FIGO I-II stage (p=0.017). This study showed higher neovascularization in malignant tumor than borderline malignancy, and in the advanced stage (FIGO III-IV) than less advanced stage (FIGO I-II) of serous carcinomas.

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