Journal of Pathology and Translational Medicine

Original Article

The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers: Ji-Ae Lee, Hye Eun Park, Hye-Yeong Jin, Lingyan Jin, Seung Yeon Yoo, Nam-Yun Cho, Jeong Mo Bae, Jung Ho Kim, Gyeong Hoon Kang; J Pathol Transl Med. 2025;59(1):50-59. Published online October 24, 2024; DOI: https://doi.org/10.4132/jptm.2024.09.26

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Abstract PDF Supplementary Material: Background
Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC.
Methods
Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method.
Results
CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]).
Conclusions
Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

Case Study

TTF1-positive SMARCA4/BRG1 deficient lung adenocarcinoma: Anurag Mehta, Himanshi Diwan, Divya Bansal, Manoj Gupta; J Pathol Transl Med. 2022;56(1):53-56. Published online November 16, 2021; DOI: https://doi.org/10.4132/jptm.2021.09.16

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SMARCA4/BRG1-deficient lung adenocarcinoma (SD-LUAD) is being recognized as a distinct subtype based on subtle differences in its clinical, morphological, and immunophenotypic attributes compared to other non–small cell lung carcinomas. We present here a case of SD-LUAD with curious thyroid transcription factor 1 (TTF1) expression in a morphologically heterogenous lung adenocarcinoma. The better differentiated area showed preservation of TTF1 expression, and a poorly differentiated tumor had loss of TTF1 expression with universal BRG1 loss.

Citations

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SMARCA4-deficient Non–small Cell Lung Cancer on 18F-FDG PET/CT
Tao Liu, Hengshan Ji, Siyuan Jiang, Rongxin Qi, Xiaodie Zhou, Jingjing Sun, Jiang Wu
Clinical Nuclear Medicine Open.2025;[Epub] CrossRef
One Case of Non-Small Cell Lung Cancer with SMARCA4 Deletion Was Reported
允龙宋
Medical Diagnosis.2024; 14(01): 137. CrossRef
Delineation of a SMARCA4-specific competing endogenous RNA network and its function in hepatocellular carcinoma
Lei Zhang, Ting Sun, Xiao-Ye Wu, Fa-Ming Fei, Zhen-Zhen Gao
World Journal of Clinical Cases.2022; 10(29): 10501. CrossRef
Novel germline SMARCA4 mutation in Small Cell Carcinoma of the Ovary, Hypercalcemic Type
Anurag Mehta, Himanshi Diwan, Diksha Karki, Divya Bansal, Meenakshi Kamboj, Anila Sharma, Shrinidhi Nathany, Sakshi Mattoo, Dushyant Kumar
Current Problems in Cancer: Case Reports.2022; 8: 100205. CrossRef

Original Articles

Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non–small cell lung carcinoma: Tripti Nakra, Varsha Singh, Aruna Nambirajan, Prabhat Singh Malik, Anant Mohan, Deepali Jain; J Pathol Transl Med. 2021;55(4):279-288. Published online July 8, 2021; DOI: https://doi.org/10.4132/jptm.2021.05.10

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Abstract PDF

Background
Thyroid transcription factor (TTF-1) is a diagnostic marker expressed in 75%–85% of primary lung adenocarcinomas (ACs). Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene is the most common targetable driver alteration in lung AC. Previous studies have shown a positive correlation between TTF-1 and EGFR mutation status. We aimed to determine the predictive value of TTF-1 immunoexpression for underlying EGFR mutation status in a large Indian cohort.
Methods
This retrospective designed study was conducted with medical record data from 2011 to 2020. All cases of primary lung AC and non–small cell lung carcinoma not otherwise specified (NSCLC, NOS) with known TTF-1 expression diagnosed by immunohistochemistry using 8G7G3/1 antibodies and EGFR mutation status diagnosed by quantitative polymerase chain reaction were retrieved, reviewed, and the
results
were analyzed. Results: Among 909 patient samples diagnosed as lung AC and NSCLC, NOS, TTF-1 was positive in 76.8% cases (698/909) and EGFR mutations were detected in 29.6% (269/909). A strong positive correlation was present between TTF-1 positivity and EGFR mutation status (odds ratio, 3.61; p < .001), with TTF-1 positivity showing high sensitivity (90%) and negative predictive value (87%) for EGFR mutation. TTF-1 immunoexpression did not show significant correlation with uncommon/dual EGFR mutations (odds ratio, 1.69; p = .098). EGFR–tyrosine kinase inhibitor therapy was significantly superior to chemotherapy among EGFR mutant cases irrespective of TTF-1 status; however, no significant differences among survival outcomes were observed.
Conclusions
Our study confirms a strong positive correlation between TTF-1 expression and common EGFR mutations (exon 19 deletion and exon 21 L858R) in advanced lung AC with significantly high negative predictive value of TTF-1 for EGFR mutations.

Citations

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Baseline retinoblastoma transcriptional corepressor 1 (Rb1) functional inactivation is a pre-requisite but not sufficient for small-cell histological transformation in epidermal growth factor receptor (EGFR) mutant lung adenocarcinomas post-tyrosine kinas
Aruna Nambirajan, Amber Rathor, Hemavathi Baskarane, Anju GS, Sachin Khurana, Somagattu Sushmitha, Aparna Sharma, Prabhat Singh Malik, Deepali Jain
Virchows Archiv.2025;[Epub] CrossRef
Mutation profile and programmed death ligand 1 status of patients with non‐small cell lung cancer diagnosed with “adenocarcinoma” and “non‐small cell carcinoma favor adenocarcinoma”
Naoko Shigeta, Tomoyuki Yokose, Shuji Murakami, Tetsuya Isaka, Kanako Shinada, Emi Yoshioka, Atsuya Narita, Kengo Katakura, Tetsuro Kondo, Terufumi Kato, Takuya Nagashima, Haruhiro Saito, Hiroyuki Ito
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Huiyue Lin, Juyong Wang, Qing Shi, Minmin Wu
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TTF-1 is a highly sensitive but not fully specific marker for pulmonary and thyroidal cancer: a tissue microarray study evaluating more than 17,000 tumors from 152 different tumor entities
Katharina Möller, Tayyaba Gulzar, Maximilian Lennartz, Florian Viehweger, Martina Kluth, Claudia Hube-Magg, Christian Bernreuther, Ahmed Abdulwahab Bawahab, Ronald Simon, Till S. Clauditz, Guido Sauter, Ria Schlichter, Andrea Hinsch, Simon Kind, Frank Jac
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Xiaoya Zhang, Junhong Meng, Mingyue Gao, Cheng Gong, Cong Peng, Duxian Liu
BMC Cancer.2024;[Epub] CrossRef
Expression landscapes in non-small cell lung cancer shaped by the thyroid transcription factor 1
Herdee Gloriane C. Luna, Marcelo Severino Imasa, Necy Juat, Katherine V. Hernandez, Treah May Sayo, Gloria Cristal-Luna, Sheena Marie Asur-Galang, Mirasol Bellengan, Kent John Duga, Bien Brian Buenaobra, Marvin I. De los Santos, Daniel Medina, Jamirah Sam
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Malignant pleural effusion cell blocks are reliable resources for PD-L1 analysis in advanced lung adenocarcinomas: a concordance study with matched histologic samples
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PLAG1, SOX10, and Myb Expression in Benign and Malignant Salivary Gland Neoplasms: Ji Hyun Lee, Hye Ju Kang, Chong Woo Yoo, Weon Seo Park, Jun Sun Ryu, Yuh-Seog Jung, Sung Weon Choi, Joo Yong Park, Nayoung Han; J Pathol Transl Med. 2019;53(1):23-30. Published online November 14, 2018; DOI: https://doi.org/10.4132/jptm.2018.10.12

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Abstract PDF

Background
Recent findings in molecular pathology suggest that genetic translocation and/oroverexpression of oncoproteins is important in salivary gland tumorigenesis and diagnosis. Weinvestigated PLAG1, SOX10, and Myb protein expression in various salivary gland neoplasm tissues.
Methods
A total of 113 cases of surgically resected salivary gland neoplasms at the NationalCancer Center from January 2007 to March 2017 were identified. Immunohistochemical stainingof PLAG1, SOX10, and Myb in tissue samples was performed using tissue microarrays.
Results
Among the 113 cases, 82 (72.6%) were benign and 31 (27.4%) were malignant. PLAG1 showednuclear staining and normal parotid gland was not stained. Among 48 cases of pleomorphicadenoma, 29 (60.4%) were positive for PLAG1. All other benign and malignant salivary glandneoplasms were PLAG1-negative. SOX10 showed nuclear staining. In normal salivary gland tissuesSOX10 was expressed in cells of acinus and intercalated ducts. In benign tumors, SOX10 expressionwas observed in all pleomorphic adenoma (48/48), and basal cell adenoma (3/3), but not inother benign tumors. SOX10 positivity was observed in nine of 31 (29.0%) malignant tumors.Myb showed nuclear staining but was not detected in normal parotid glands. Four of 31 (12.9%)malignant tumors showed Myb positivity: three adenoid cystic carcinomas (AdCC) and onemyoepithelial carcinoma with focal AdCC-like histology.
Conclusions
PLAG1 expression is specificto pleomorphic adenoma. SOX10 expression is helpful to rule out excretory duct origin tumor,but its diagnostic value is relatively low. Myb is useful for diagnosing AdCC when histology isunclear in the surgical specimen.

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Case Study

Aggressive Supratentorial Ependymoma, RELA Fusion-Positive with Extracranial Metastasis: A Case Report: Seong-Ik Kim, Yoojin Lee, Seung Ki Kim, Hyoung Jin Kang, Sung-Hye Park; J Pathol Transl Med. 2017;51(6):588-593. Published online November 15, 2017; DOI: https://doi.org/10.4132/jptm.2017.08.10

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Abstract PDF

Ependymoma is the third most common pediatric primary brain tumor. Ependymomas are categorized according to their locations and genetic abnormalities, and these two parameters are important prognostic factors for patient outcome. For supratentorial (ST) ependymomas, RELA fusion-positive ependymomas show a more aggressive behavior than YAP1 fusion-positive ependymomas. Extracranial metastases of intra-axial neuroepithelial tumors are extremely rare. In this paper, we report a case of aggressive anaplastic ependymoma arising in the right frontoparietal lobe, which had genetically 1q25 gain, CDKN2A homozygous deletion, and L1CAM overexpression. The patient was a 10-year-old boy who underwent four times of tumor removal and seven times of gamma knife surgery. Metastatic loci were scalp and temporalis muscle overlying primary operation site, lung, liver, buttock, bone, and mediastinal lymph nodes. He had the malignancy for 10 years and died. This tumor is a representative case of RELA fusion-positive ST ependymoma, showing aggressive behavior.

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Case report: Polymorphous low-grade neuroepithelial tumor of the young and supratentorial ependymoma diagnosed in an adult male
Cynthia Y. Xu, Craig A. Beers, Jian-Qiang Lu, Crystal L. Hann, Ronald C. Ramos
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A Pediatric Case of Extraneural Subcutaneous Metastasis of Ependymoma
Chika Ueno, Masayuki Tanaka, Ayako Yamazaki, Shuichi Yamamoto
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Patterns of Extraneural Metastases in Children With Ependymoma
Priya P. Chan, Nicholas S. Whipple, Biswarathan Ramani, David A. Solomon, Holly Zhou, Luke L. Linscott, John R.W. Kestle, Carol S. Bruggers
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Magnetic Resonance Imaging Features of Zinc Finger Translocation Associated-RELA Fusion Ependymoma Compared to Its Wild-Type Counterpart
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A clinicopathological analysis of supratentorial ependymoma, ZFTA fusion-positive: utility of immunohistochemical detection of CDKN2A alterations and characteristics of the immune microenvironment
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Mutation profiling of anaplastic ependymoma grade III by Ion Proton next generation DNA sequencing
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Epithelial-to-mesenchymal transition–related transcription factors are up-regulated in ependymomas and correlate with a poor prognosis
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Original Articles

The Role of TWIST in Ovarian Epithelial Cancers: Kyungbin Kim, Eun Young Park, Man Soo Yoon, Dong Soo Suh, Ki Hyung Kim, Jeong Hee Lee, Dong Hoon Shin, Jee Yeon Kim, Mee Young Sol, Kyung Un Choi; Korean J Pathol. 2014;48(4):283-291. Published online August 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.4.283

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Abstract PDF

Background

Epithelial-mesenchymal transition (EMT) is associated with tumor hypoxia. EMT is regulated, in part, by the action of TWIST, which inhibits of E-cadherin expression and may interfere with the p53 tumor-suppressor pathway.

Methods

We examined the expression of TWIST, E-cadherin, hypoxia-inducible factor 1α (HIF1α), and p53 by immunohistochemistry in 123 cases of ovarian epithelial cancers (OEC) to evaluate the role of TWIST in OEC. We assessed the association between protein expression and clinicopathologic parameters.

Results

The expression of TWIST, E-cadherin, HIF1α, and p53 proteins was found in 28.5%, 51.2%, 35.0%, and 29.3% of cases, respectively. TWIST expression was associated with higher histologic grade and unfavorable survival. TWIST expression was correlated with HIF1α expression and reduced E-cadherin expression. The altered HIF1α/TWIST/E-cadherin pathway was associated with lower overall survival (OS), while the co-expression of TWIST and p53 was correlated with lower progression-free survival. In the multivariate analyses, TWIST expression was an independent prognostic factor for OS.

Conclusions

Our data imply that TWIST expression could be a useful predictor of unfavorable prognosis for OEC. TWIST may affect the p53 tumor-suppressor pathway. Moreover, hypoxia-mediated EMT, which involves the HIF1α/TWIST/E-cadherin pathway may play an important role in the progression of OEC.

Citations

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The Mechanism and Dynamic Regulation of Epithelial to Mesenchymal Transition in Ovarian Cancer
Pande Kadek Aditya Prayudi, I Gde Sastra Winata, I Nyoman Bayu Mahendra, I Nyoman Gede Budiana, Kade Yudi Saspriyana, Ketut Suwiyoga
Clinical and Experimental Obstetrics & Gynecology.2023;[Epub] CrossRef
E-Cadherin Expression in Relation to Clinicopathological Parameters and Survival of Patients with Epithelial Ovarian Cancer
Michal Kielbik, Izabela Szulc-Kielbik, Magdalena Klink
International Journal of Molecular Sciences.2022; 23(22): 14383. CrossRef
Oxygen sensing, mitochondrial biology and experimental therapeutics for pulmonary hypertension and cancer
Danchen Wu, Asish Dasgupta, Austin D. Read, Rachel E.T. Bentley, Mehras Motamed, Kuang-Hueih Chen, Ruaa Al-Qazazi, Jeffrey D. Mewburn, Kimberly J. Dunham-Snary, Elahe Alizadeh, Lian Tian, Stephen L. Archer
Free Radical Biology and Medicine.2021; 170: 150. CrossRef
Hypoxia-Induced Epithelial-Mesenchymal Transition in Cancers: HIF-1α and Beyond
Shing Yau Tam, Vincent W. C. Wu, Helen K. W. Law
Frontiers in Oncology.2020;[Epub] CrossRef
Expression of selected epithelial–mesenchymal transition transcription factors in serous borderline ovarian tumors and type I ovarian cancers
Pawel Sadlecki, Jakub Jóźwicki, Paulina Antosik, Marek Grabiec
Tumor Biology.2018; 40(6): 101042831878480. CrossRef
Expression and prognostic significance of epithelial-mesenchymal transition-related markers and phenotype in serous ovarian cancer
In Hye Song, Kyu-Rae Kim, Sehun Lim, Seok-Hyung Kim, Chang Ohk Sung
Pathology - Research and Practice.2018; 214(10): 1564. CrossRef
Transcription factors controlling E-cadherin down-regulation in ovarian cancer
Holly Russell, Md Zahidul Islam Pranjol
Bioscience Horizons: The International Journal of Student Research.2018;[Epub] CrossRef
Immunohistochemical expression of TWIST in oral squamous cell carcinoma and its correlation with clinicopathologic factors
Maryam Seyedmajidi, Safoura Seifi, Dariush Moslemi, Seyyedeh-Fatemeh Mozaffari, Hemmat Gholinia, Zahra Zolfaghari
Journal of Cancer Research and Therapeutics.2018; 14(5): 964. CrossRef
Activation of TWIST1 by COL11A1 promotes chemoresistance and inhibits apoptosis in ovarian cancer cells by modulating NF‐κB‐mediated IKKβ expression
Yi‐Hui Wu, Yu‐Fang Huang, Tzu‐Hao Chang, Cheng‐Yang Chou
International Journal of Cancer.2017; 141(11): 2305. CrossRef
MicroRNA-219-5p inhibits the proliferation, migration, and invasion of epithelial ovarian cancer cells by targeting the Twist/Wnt/β-catenin signaling pathway
Chunyan Wei, Xi Zhang, Sai He, Bianli Liu, Hongfang Han, Xuejun Sun
Gene.2017; 637: 25. CrossRef
Inhibition of proliferation and invasion of hepatocellular carcinoma cells by lncRNA-ASLNC02525 silencing and the mechanism
Zi Chen, Dongwen Xu, Tao Zhang
International Journal of Oncology.2017; 51(3): 851. CrossRef
Is overexpression of TWIST, a transcriptional factor, a prognostic biomarker of head and neck carcinoma? Evidence from fifteen studies
Xianlu Zhuo, Huanli Luo, Aoshuang Chang, Dairong Li, Houyu Zhao, Qi Zhou
Scientific Reports.2015;[Epub] CrossRef

Expression of CHOP in Squamous Tumor of the Uterine Cervix: Hyun Hee Chu, Jun Sang Bae, Kyoung Min Kim, Ho Sung Park, Dong Hyu Cho, Kyu Yun Jang, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee, Myoung Ja Chung; Korean J Pathol. 2012;46(5):463-469. Published online October 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.5.463

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Abstract PDF

Background

High-risk human papillomavirus (HR-HPV) infection and abnormal p53 expression are closely involved in carcinogenesis of squamous cell carcinoma (SqCC) of uterine cervix. Recent studies have suggested that virus-induced endoplasmic reticulum (ER) stress modulates various cell survival and cell death signaling pathways. The C/EBP homologous protein (CHOP) is associated with ER stress-mediated apoptosis and is also involved in carcinogenesis of several human cancers. We hypothesized that CHOP is involved in the carcinogenesis of uterine cervical cancer in association with HR-HPV and/or p53.

Methods

Immunohistochemistry was used to analyze CHOP and p53 protein expression of tissue sections from 191 patients with invasive cancer or preinvasive lesions of the uterine cervix (61 cases of SqCC, 66 cases of cervical intraepithelial neoplasia [CIN] III, and 64 cases of CIN I).

Results

CHOP was expressed in 59.4% of CIN I, 48.5% of CIN III, and 70.5% of SqCC cases. It was also significantly more frequent in invasive SqCC than in preinvasive lesions (p=0.042). Moreover, CHOP expression significantly correlated with HR-HPV infection and p53 expression (p=0.009 and p=0.038, respectively).

Conclusions

Our results suggest that CHOP is involved in the carcinogenesis of the uterine cervix SqCC via association with HR-HPV and p53.

Citations

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Expression of GRP78 and its copartners in HEK293 and pancreatic cancer cell lines (BxPC-3/PANC-1) exposed to MRI and CT contrast agents
Ali Ahmed Azzawri, Ibrahim Halil Yildirim, Zeynep Yegin, Abdurrahim Dusak
Nucleosides, Nucleotides & Nucleic Acids.2024; 43(5): 391. CrossRef
Endoplasmic Reticulum Stress and Homeostasis in Reproductive Physiology and Pathology
Elif Guzel, Sefa Arlier, Ozlem Guzeloglu-Kayisli, Mehmet Tabak, Tugba Ekiz, Nihan Semerci, Kellie Larsen, Frederick Schatz, Charles Lockwood, Umit Kayisli
International Journal of Molecular Sciences.2017; 18(4): 792. CrossRef
Endoplasmic reticulum stress pathway PERK‐eIF2α confers radioresistance in oropharyngeal carcinoma by activating NF‐κB
Qiao Qiao, Chaonan Sun, Chuyang Han, Ning Han, Miao Zhang, Guang Li
Cancer Science.2017; 108(7): 1421. CrossRef
Curcumin induces ER stress-mediated apoptosis through selective generation of reactive oxygen species in cervical cancer cells
Boyun Kim, Hee Seung Kim, Eun-Ji Jung, Jung Yun Lee, Benjamin K. Tsang, Jeong Mook Lim, Yong Sang Song
Molecular Carcinogenesis.2016; 55(5): 918. CrossRef
Down-regulation of C/EBP homologous protein (CHOP) expression in gastric cardia adenocarcinoma: Their relationship with clinicopathological parameters and prognostic significance
Xiao-Juan Zhu, She-Gan Gao, San-Qiang Li, Zhen-Guo Shi, Zhi-Kun Ma, Shan-Shan Zhu, Xiao-Shan Feng
Clinics and Research in Hepatology and Gastroenterology.2015; 39(3): 391. CrossRef
MG289 in <i>Mycoplasma genitalium</i> Enhances Microbial Invasion and Bacterial Persistence in Benign Human Prostate Cells
Wasia Rizwani, Leticia Reyes, Jeongsoon Kim, Steve Goodison, Charles J. Rosser
Open Journal of Urology.2013; 03(06): 232. CrossRef

Expression of Hepatocyte Growth Factor/c-met by RT-PCR in Meningiomas.: Na Rae Kim, Yang Seok Chae, Weon Jeong Lim, Seong Jin Cho; Korean J Pathol. 2011;45(5):463-468.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.463

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Abstract PDF: BACKGROUND
Hepatocyte growth factor (HGF) is a potent mitogenic cytokine. C-met protein, which is known to be the HGF receptor has transmembrane tyrosine kinase activity and is encoded by the c-met oncogene. The HGF/c-met signaling pathway may play various roles in the carcinogenesis of various organs.
METHODS
We examined HGF and c-met mRNA expression by utilizing reverse transcription polymerase chain reaction on 40 surgically resected intracranial meningiomas (25 benign, 10 atypical, and 5 anaplastic cases).
RESULTS
An HGF overexpression was detected in 28%, 50%, and 80% of the benign, atypical and anaplastic meningiomas, respectively; a high expression of HGF or the coexpression of HGF/c-met was detected in the high grade meningiomas (the atypical and anaplastic cases, p=0.046, p=0.014). An HGF expression was statistically significant in the recurrent meningiomas (p=0.003), and HGF expression was significantly lower than c-met mRNA expression in benign meningiomas (p=0.034).
CONCLUSIONS
There was no correlation between histologic subtypes and HGF/c-met expression. Determination of HGF expression can be used as a molecular predictor for recurrence of meningioimas. These results suggest that HGF and c-met expression in meningiomas may be associated with anaplastic progression.

Enhanced Protein Expression of Signal Transducer and Activator of Transcription 3 and Protein Kinase Substrate p36 in Hepatocellular Carcinoma.: Hongxiu Han, Si Hyong Jang, Chan Kum Park; Korean J Pathol. 2009;43(5):393-399.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.393

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Abstract PDF: BACKGROUND
Signal transducers and activators of transcription 3 (STAT3) and protein kinase substrate p36 may be involved in cell proliferation, differentiation and growth.
METHODS
Immunohistochemistry for STAT3 and p36 was performed in 46 patients with hepatocellular carcinoma (HCC).
RESULTS
STAT3 staining was present in the cytoplasm and/or nucleus, while p36 staining was present in the nucleus. STAT3 and p36 expression occurred in 78.3% (36/46) and 47.8% (22/46) of HCC patients, respectively. However, no correlation was found between STAT3 and p36 protein expression (p>0.05). Enhanced expression of STAT3 was negatively correlated with portal vein invasion (p=0.033). Expression of STAT3 in the nucleus was correlated with tumor grade (p=0.004). Enhanced expression of p36 was correlated with tumor grade (p=0.031). HCC was correlated with HBV infection (p=0.032). The patients'5-year survival was related to expression of p36 (p=0.044), but not to total STAT3 or nuclear STAT3 (p>0.05).
CONCLUSIONS
The enhanced expression of STAT3 in the nucleus and the enhanced expression of p36 are associated with the aggressive phenotype of HCC. Enhanced p36 expression may contribute to poor survival of patients with HCC.

The Expressions of E2F1 and p53 in Gastrointestinal Stromal Tumors and Their Prognostic Significance.: Mi Jung Kwon, Eun Sook Nam, Seong Jin Cho, Hye Rim Park, Hyung Sik Shin, Jong Seok Lee, Chan Heun Park, Woon Geon Shin; Korean J Pathol. 2009;43(3):212-220.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.3.212

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Abstract PDF

BACKGROUND
E2F1 plays a critical role in the G1-to-S phase transition by inducing various genes that encode S phase-activating proteins and that modulate such diverse cellular functions as DNA synthesis, mitosis and apoptosis. The purpose of this study was to assess the E2F1 expression in relation to the clinicopathologic parameters and other tumor markers in gastrointestinal stromal tumors.
METHODS
Immunohistochemical stainings for obtaining the E2F1, p53, and Ki-67 labeling indices were performed on a tissue microarray of 72 gastrointestinal stromal tumor specimens. The clinicopathologic parameters that were analyzed including the risk grade system by Miettinen et al. and the disease-free survival (DFS) rate.
RESULTS
1) An E2F1 expression was correlated with a larger tumor size, a p53 expression and a shorter period of DFS (p=0.014, p=0.007, and p=0.039). 2) A p53 expression was significantly associated with a high risk grade, a larger tumor size, high mitotic counts and a shorter period of DFS (p=0.003, p=0.044, p<0.001, and p<0.0001). 3) A high-risk grade and the epithelioid type were significantly associated with a shorter period of DFS (p=0.0006 and p=0.0008).
CONCLUSIONS
E2F1, as well as p53, may be a potentially novel independent prognostic factor for predicting a worse outcome for those patients suffering with Gastrointestinal stromal tumors.

Citations

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Comparison of tissue microarray and full section in immunohistochemistry of gastrointestinal stromal tumors
Mi Jung Kwon, Eun Sook Nam, Seong Jin Cho, Hye Rim Park, Hyung Sik Shin, Jun Ho Park, Chan Heun Park, Won Jae Lee
Pathology International.2009; 59(12): 851. CrossRef

mRNA is Synthesized Mainly at the Phase between the Euchromatin and Heterochromatin: Proposal of a Phase Theory.: Mi Sook Kim, Sang Woo Juhng; Korean J Pathol. 2001;35(2):93-97.

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Abstract PDF: BACKGROUND
Malignant cell nuclei, in general, have increased amounts of heterochromatin and decreased electron densities of euchromatin, making the chromatin pattern coarser than that of benign cell nuclei. The chromatin pattern in benign and malignant cells, however, is barely explained in terms of molecular structure. In this study, the chromatin pattern of metaplastic and carcinomatous squamous cells of the uterine cervix was correlated with transcriptional activity by ultrastructural autoradiography. METHODS: Punch-biopsied tissues were cultured with 3H-uridine for 5 minutes and processed for electron microscopy. Thin sections of the tissues on nickel grids were covered with photosensitive emulsion and kept cold in a dark room for 10 to 16 weeks. After development and staining, the tissues were observed by electron microscopy.
RESULTS
The nuclei of the metaplastic squamous cells consisted mostly of euchromatin. A few silver grains were observed, mainly at the periphery of the nuclei. The nuclei of the carcinomatous cells had increased amounts of heterochromatin along the nuclear membrane, and also in the euchromatin area. Silver grains were observed mainly at the boundary between the heterochromatin and euchromatin.
CONCLUSION
These findings suggest that an increased amount of heterochromatin in carcinomatous cells results in an increase of the boundary area between the heterochromatin and euchromatin, an area which may be a transcriptionally active site.

Immunoexpressions of Thyroid Transcription Factor-1 and bcl-2 in Congenital Cystic Adenomatoid Malformation.: Na Rae Kim, Dong Hoon Kim, Gou Young Kim, Dae Shick Kim, Joungho Han; Korean J Pathol. 2003;37(1):10-14.

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Abstract PDF: BACKGROUND
Congenital cystic adenomatoid malformation (CCAM) is a congenital abnormality of branching morphogenesis of the lung. Thyroid transcription factor-1 (TTF-1) is detected in human respiratory epithelial cells from 11 weeks of gestation, and at full term, TTF-1 expression is confined within type II epithelial cells and in some respiratory nonciliated bronchiolar epithelial cells. Immunoexpression of bcl-2 is intimately related to apoptosis during the development.
METHODS
To elucidate the nature of the lesion, TTF-1 expression was evaluated in twenty-four cases of CCAM (eight cases of type 1 and sixteen cases of type 2) along with immunostaining for bcl-2. For the control group, four cases of fetal lungs (19 week-, 21 week-, 27 week- and 40 week-gestational age) were also evaluated. In all cases of CCAM, TTF-1 was detected in the nuclei of epithelial cells lining the cysts.
RESULTS
TTF-1 was expressed in the majority of the bronchiolar-like epithelial cells of the cysts in CCAM types 1, and 2, where almost 100% of the lining cells of the cysts were TTF-1 positive with variable intensity, while negative TTF-1 expressions were found in the alveolar-like epithelium of the adjacent alveoli or distal nonciliated bronchi. For bcl-2 immunostaining, no lining epithelial cells of the cysts were stained except for the infiltrating lymphocytes. In the control group, strong immunoreactivities found in early fetal stages were absent in the full-term aged lung (40 gestational weeks).
CONCLUSION
These results support the hypothesis that CCAM types 1 and 2 reflect the abnormalities in lung morphogenesis and differentiation that are distinct from those for normally developed alveolar epithelium or adjacent bronchial epithelium, thus retaining the abnormal TTF-1 immunoreactions. Though restricted to CCAM types 1 and 2 in this study, CCAM might be related to TTF-1 rather than apoptosis in the morphogenesis of the developing lung.

Case Report

Uterine Cervical Large Cell Neuroendocrine Carcinoma Concurrent with High Grade Squamous Intraepithelial Neoplasia: A Case Report.: Yun Kyung Kang, Jae Whoan Koh; Korean J Pathol. 2008;42(6):389-392.

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Abstract PDF: Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is a rare and aggressive malignancy. We report a case of uterine cervical LCNEC concurrent with high grade squamous intraepithelial neoplasia (HG-SIN). The LCNEC expressed chromogranin A and thyroid transcription factor 1 (TTF1). The HG-SIN was negative for these markers. Human papillomavirus (HPV) type 18 was positive in LCNEC whereas both type 16 and 18 were positive in HG-SIN by nested polymerase chain reaction. This case showed TTF1 positivity nonetheless diagnosed as a primary uterine cervical LCNEC confirmed by the detection of HPV genome within the tumor. It is critical to recognize LCNEC of the uterine cervix even in the small biopsy specimen because it is a distinctive clinicopathological entity with highly aggressive behavior and unfavorable outcome.

Original Articles

The Differential Expressions of the Epithelial-Mesenchymal Transition Regulator, Slug and the Cell Adhesion Molecule, E-cadherin in Colorectal Adenocarcinoma.: Ran Hong, Dong Yul Choi, Sung Chul Lim, Chae Hong Suh, Keun Hong Kee, Mi Ja Lee; Korean J Pathol. 2008;42(6):351-357.

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Abstract PDF: BACKGROUND
Slug is a member of the Snail family of transcription factors, and it plays a crucial role in the regulation of the epithelial-mesenchymal transition by suppression of several epithelial proteins and adhesion molecules, including E-cadherin. METHODS: The aim of the present study was to examine the significance between the expression of Slug in colorectal adenocarcinoma (CRA) specimens and the clinicopathological parameters of CRA, as determined by immunohistochemical analysis, and to determine the correlation between the Slug and E-cadherin expressions in non-neoplastic colorectal mucosa (n=45), primary CRA (n= 109) and metastatic CRA (n=17). A semiquantitative scoring system was applied based on the intensity and extent of the positive immunohistochemical staining. RESULTS: The expressions of Slug and E-cadherin were associated with the depth of tumor invasion (pT) (p=0.019, p=0.001, respectively), and these expressions showed a significant inverse correlation (p<0.001) each other. CONCLUSIONS: Our results demonstrated a positive role for Slug in the development of CRA, and Slug is a mediator of tumor invasion in CRA. In addition, an up-regulated Slug expression is significantly correlated with the loss of an E-cadherin expression, which suggests that Slug may play some role in the epithelial-mesenchymal transition (EMT) by down-regulating the E-cadherin expression.

Twist Expression in Upper Urinary Tract Urothelial Carcinoma Affects Patients Disease Free Survival and is Associated with Tumor Grade.: Dong Il Kim, Sun Och Yoon, Seog Yun Park, Bomi Kim, Gyeong Hoon Kang, Kyung Chul Moon; Korean J Pathol. 2007;41(5):324-328.

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Abstract PDF: BACKGROUND
Epithelial-mesenchymal transition (EMT) is critical for morphogenesis during embryonic development and is also implicated in the conversion of early-stage tumors into invasive malignancies. Recently, Twist has been identified to play an important role in EMTmediated metastatic progression of several types of human cancer. The present study examined the expression of Twist and evaluated its clinicopathologic significance in urothelial carcinoma of upper urinary tract.
METHODS
Immunohistochemical staining for Twist expression was performed on 70 upper urinary tract urothelial carcinomas (UUT-UCs) using tissue microarray.
RESULTS
Immunohistochemical staining for Twist was positive in 31/70 cases (44.3%) of UUT-UCs. Twist expression was associated with high-grade and advanced-stage (ISUP grade, p<0.01; stage, p=0.045). The patients with Twist positive-tumors revealed lower disease free survival rate than those with Twist negative-tumors (p<0.01). The overall survival for patients with Twist positive-tumors was slightly worse than the patients with Twist negative- tumors, but the difference was not statistically significant (p=0.12).
CONCLUSION
Our results suggest that Twist is a novel marker for advanced UUT-UC.

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