Journal of Pathology and Translational Medicine

Case Study

Hepatic small vessel neoplasm: not totally benign, not yet malignant: Madison Miranda, David Howell, Tony El Jabbour; J Pathol Transl Med. 2023;57(5):273-277. Published online August 24, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.19

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Abstract PDF: Hepatic small vessel neoplasm (HSVN) is a rare vascular tumor with few reports in the literature. While imaging findings may show characteristic enhancement patterns, limited available literature may not reveal the full potential for image-based diagnosis. Histologically, HSVN mimics other entities, though certain morphologic and immunohistochemical findings provide clues for diagnosis. However, HSVN still provides diagnostic challenges, especially on core biopsies with limited material for morphologic and molecular evaluation. While current recommendations are surgical resection and close observation, the long-term course of the tumor is unknown. We report a case of HSVN in a liver with additional feature of organized lymphoid aggregates necessitating additional hematopathology consultation and workup to rule out concurrent entities.

Original Articles

High Expression of Galectin-1, VEGF and Increased Microvessel Density Are Associated with MELF Pattern in Stage I-III Endometrioid Endometrial Adenocarcinoma: Dmitry Aleksandrovich Zinovkin, Sergey Leonidovich Achinovich, Mikhail Grigoryevich Zubritskiy, Jacqueline Linda Whatmore, Md Zahidul Islam Pranjol; J Pathol Transl Med. 2019;53(5):280-288. Published online June 27, 2019; DOI: https://doi.org/10.4132/jptm.2019.05.13

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Background
In this study, we investigate the expression of markers of angiogenesis and microvessel density (MVD) in cases of microcystic, elongated and fragmented (MELF) pattern, with its prognostic role in the survival of endometrioid endometrial adenocarcinomas (EA) patients.
Methods
In this study, 100 cases of EA, 49 cases with MELF pattern and 51 without, were immunohistochemically stained for galectin-1, vascular endothelial growth factor (VEGF), and MVD. Morphometry and statistical (univariate and multivariate) analyses were performed to assess overall survival (OS) and disease-free survival.
Results
The expression of VEGF (p<.001) and galectin-1 (p<.001), as well as MVD area (p<.001) and number of vessels/mm2 (p<.050), were significantly higher in the +MELF pattern group compared to the –MELF group. A low negative correlation between MELFpattern and the number of days of survival (p<.001, r=–0.47) was also found. A low positive correlation of MELF-pattern with galectin-1 expression (p<.001, r=0.39), area of vessels/mm2 (p<.001, r=0.36), outcome of EA (p<.001, r=0.42) and VEGF expression (p<.001, r=0.39) suggests potential pathological relevance of these factors in the prognosis of EA. A univariate survival analysis indicated a role for all parameters of survival. Multivariate Cox proportional hazard regression analysis revealed that only area of vessels/mm2 (hazard ratio [HR], 1.018; 95% confidence interval [CI], 1.002 to 1.033), galectin-1 (HR, 1.049; 95% CI, 1.025 to 1.074) and VEGF (HR, 1.049; 95% CI, 1.022 to 1.077) play key roles in OS.
Conclusions
This study reports an increase in MVD, VEGF and galectin-1 expression in EA with MELF pattern and suggests that MELF pattern, along with the angiogenic profile, may be a prognostic factor in EA.

Citations

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Determining the level of stromal and epithelial cells activity in normal and hyperplastic endometrium of late reproductive and perimenopausal women
Zinaida Vasilyvna Chumak, Volodymyr Victorovich Artyomenko, Mykola Vitaliiovich Shapoval, Liudmyla Volodymyrivna Mnih, Ganna Volodymyrivna Kozhukhar, Serhii Vasilyovich Derishov
Journal of Medicine and Life.2023; 16(2): 210. CrossRef
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Hyunsik Bae, Hyun-Soo Kim
Biomedicines.2023; 11(11): 3026. CrossRef
Clinicopathologic association and prognostic impact of microcystic, elongated and fragmented pattern invasion, combined with tumor budding in endometrioid endometrial cancer
Xiqin Qi, Lun Zhu, Bei Zhang
Journal of Obstetrics and Gynaecology Research.2022; 48(9): 2431. CrossRef
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Ran Li, Fang Dong, Ling Zhang, Xiuqin Ni, Guozhi Lin
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Emilie Alard, Aura-Bianca Butnariu, Marta Grillo, Charlotte Kirkham, Dmitry Aleksandrovich Zinovkin, Louise Newnham, Jenna Macciochi, Md Zahidul Islam Pranjol
Cancers.2020; 12(7): 1826. CrossRef

The Potential Roles of MELF-Pattern, Microvessel Density, and VEGF Expression in Survival of Patients with Endometrioid Endometrial Carcinoma: A Morphometrical and Immunohistochemical Analysis of 100 Cases: Dmitry Aleksandrovich Zinovkin, Md Zahidul Islam Pranjol, Daniil Rudolfovich Petrenyov, Eldar Arkadievich Nadyrov, Oleg Gennadievich Savchenko; J Pathol Transl Med. 2017;51(5):456-462. Published online September 14, 2017; DOI: https://doi.org/10.4132/jptm.2017.07.19

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Abstract PDF

Background
In this study, we hypothesized that microcystic, elongated, fragmented (MELF)-pattern, vascular endothelial growth factor (VEGF) expression by cancer cells and microvessel density of cancer stroma may be associated with progression of endometrioid adenocarcinoma. Methods: The study used data from the Belarus Cancer Registry and archival histological material of 100 patients with retrospectively known good (survival) and poor (disease progression and death) outcomes. All cases were immunohistochemically stained for CD34 and VEGF. Two independent samples were compared for the characteristics of signs, and obtained results were analyzed by receiver operating characteristic analysis, Mann-Whitney U test, χ² test (Yates correction), and Mantel-Cox test. Multivariate Cox hazard analysis and Spearman correlation test were used. A p-value of less than .05 was considered statistically significant. Results: The observed survival rate of patients with endometrioid adenocarcinoma was significantly lower (p = .002) in MELF-pattern positive patients when compared with MELF-pattern negative patients. The overall survival rate of patients whose tumors had more than 114 vessels/mm² of tissue was significantly low (p < .001). Interestingly, a similar observation was found in patients with increased vessel area, evidenced by VEGF expression in the glandular tumor component. Conclusions: Our study suggests, for the first time, that these criteria may be used as risk factors of endometrioid adenocarcinoma progression during 5 years after radical surgical treatment. However, a large independent cohort of samples should be considered in the future to validate our findings.

Citations

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Molecular Classification of Endometrial Endometrioid Carcinoma With Microcystic Elongated and Fragmented Pattern
Baohui Ju, Jianghua Wu, Lin Sun, Chunrui Yang, Hu Yu, Quan Hao, Jianmei Wang, Huiying Zhang
International Journal of Gynecological Pathology.2024; 43(3): 233. CrossRef
Dynamic contrast-enhanced MR imaging of uterine endometrial carcinoma with/without squamous differentiation
Mayumi Takeuchi, Kenji Matsuzaki, Yoshimi Bando, Masafumi Harada
Abdominal Radiology.2023; 48(8): 2494. CrossRef
Role of adipocytokines in endometrial cancer progression
Ran Li, Fang Dong, Ling Zhang, Xiuqin Ni, Guozhi Lin
Frontiers in Pharmacology.2022;[Epub] CrossRef
Endometrial carcinoma: use of tracer kinetic modeling of dynamic contrast-enhanced MRI for preoperative risk assessment
Zhijun Ye, Gang Ning, Xuesheng Li, Tong San Koh, Huizhu Chen, Wanjing Bai, Haibo Qu
Cancer Imaging.2022;[Epub] CrossRef
Microcystic elongated and fragmented (MELF) pattern of invasion: Molecular features and prognostic significance in the PORTEC-1 and -2 trials
A.S.V.M. van den Heerik, K.T.S. Aiyer, E. Stelloo, I.M. Jürgenliemk-Schulz, L.C.H.W. Lutgens, J.J. Jobsen, J.W.M. Mens, E.M. van der Steen-Banasik, C.L. Creutzberg, V.T.H.B.M. Smit, N. Horeweg, T. Bosse
Gynecologic Oncology.2022; 166(3): 530. CrossRef
Pathological features, immunoprofile and mismatch repair protein expression status in uterine endometrioid carcinoma: focus on MELF pattern of myoinvasion
Angela Santoro, Giuseppe Angelico, Frediano Inzani, Saveria Spadola, Damiano Arciuolo, Michele Valente, Teresa Musarra, Giovanni Capelli, Francesco Fanfani, Valerio Gallotta, Giovanni Scambia, Gian Franco Zannoni
European Journal of Surgical Oncology.2021; 47(2): 338. CrossRef
Prognostic impact of tumor budding in endometrial carcinoma within distinct molecular subgroups
Tilman T. Rau, Eva Bettschen, Carol Büchi, Lucine Christe, Amanda Rohner, Michael D. Müller, Joseph W. Carlson, Sara Imboden, Inti Zlobec
Modern Pathology.2021; 34(1): 222. CrossRef
Sentinel Nodal Metastasis Detection in Endometrial Carcinoma With Microcystic, Elongated, and Fragmented (MELF) Pattern by Cytokeratin Immunostaining
Kimmie M Rabe, Molly E Klein, Sayak Ghatak, Irina Stout, Alexandra Schefter, Britt K Erickson, Mahmoud A Khalifa
American Journal of Clinical Pathology.2021; 156(5): 846. CrossRef
Patterns of Myometrial Invasion in Endometrial Adenocarcinoma with Emphasizing on Microcystic, Elongated and Fragmented (MELF) Glands Pattern: A Narrative Review of the Literature
Svetlana Mateva, Margarita Nikolova, Angel Yordanov
Diagnostics.2021; 11(9): 1707. CrossRef
Increase in FoxP3, CD56 immune cells and decrease in glands PGRMC1 expression in the endometrium are associated with recurrent miscarriages
Yulia Anatolievna Lyzikova, Dmitry Aleksandrovich Zinovkin, Md Zahidul Islam Pranjol
European Journal of Obstetrics & Gynecology and Reproductive Biology.2020; 245: 121. CrossRef
Clinicopathologic Association and Prognostic Value of MELF Pattern in Invasive Endocervical Adenocarcinoma (ECA) as Classified by IECC
Sheila E. Segura, Lien Hoang, Monica Boros, Cristina Terinte, Anna Pesci, Sarit Aviel-Ronen, Takako Kiyokawa, Isabel Alvarado-Cabrero, Esther Oliva, Kay J. Park, Robert A. Soslow, Simona Stolnicu
International Journal of Gynecological Pathology.2020; 39(5): 436. CrossRef
Usual-Type Endocervical Adenocarcinoma with a Microcystic, Elongated, and Fragmented Pattern of Stromal Invasion: A Case Report with Emphasis on Ki-67 Immunostaining and Targeted Sequencing Results
Sangjoon Choi, Soohyun Hwang, Sung-Im Do, Hyun-Soo Kim
Case Reports in Oncology.2020; 13(3): 1421. CrossRef
High Expression of Galectin-1, VEGF and Increased Microvessel Density Are Associated with MELF Pattern in Stage I-III Endometrioid Endometrial Adenocarcinoma
Dmitry Aleksandrovich Zinovkin, Sergey Leonidovich Achinovich, Mikhail Grigoryevich Zubritskiy, Jacqueline Linda Whatmore, Md Zahidul Islam Pranjol
Journal of Pathology and Translational Medicine.2019; 53(5): 280. CrossRef
The Roles of Melf Patterns, the Depth of Invasion and Number of Tumor Emboli as the Predictive Factors of the Survival Rate Among Patients with Endometrioid Adenocarcinoma of the Corpus Uterus
D. A. Zinovkin
Health and Ecology Issues.2019; (1): 49. CrossRef
Non-endometrioid and high-grade endometrioid endometrial cancers show DNA fragmentation factor 40 (DFF40) and B-cell lymphoma 2 protein (BCL2) underexpression, which predicts disease-free and overall survival, but not DNA fragmentation factor 45 (DFF45) u
Tomasz Banas, Kazimierz Pitynski, Krzysztof Okon, Aleksandra Winiarska
BMC Cancer.2018;[Epub] CrossRef
Tumor-Associated T-Lymphocytes and Macrophages are Decreased in Endometrioid Endometrial Carcinoma with MELF-Pattern Stromal Changes
Dmitry Aleksandrovich Zinovkin, Md Zahidul Islam Pranjol, Il’ya Andreevich Bilsky, Valeriya Alexandrovna Zmushko
Cancer Microenvironment.2018; 11(2-3): 107. CrossRef
MELF pattern of myometrial invasion and role in possible endometrial cancer diagnostic pathway: A systematic review of the literature
Anastasia Prodromidou, George Vorgias, Konstantinos Bakogiannis, Nikolaos Kalinoglou, Christos Iavazzo
European Journal of Obstetrics & Gynecology and Reproductive Biology.2018; 230: 147. CrossRef
CORRELATIVE INTERRELATIONS OF THE TUMOR MICROENVIRONMENT AND RELATIVE RISK OF UNFAVOURABLE OUTCOME OF ENDOMETRIOID ADENOCARCINOMA OF THE CORPUS UTERI
D. A. Zinovkin
Health and Ecology Issues.2018; (3): 48. CrossRef

The Definition of Minimal Extrathyroid Extension in Thyroid Pathology by Analyzing Sizable Intra- and Extrathyroid Blood Vessels: Hyae Min Jeon, Beom Jin Lim, Hang-Seok Chang, SoonWon Hong; Korean J Pathol. 2012;46(6):548-553. Published online December 26, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.548

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Abstract PDF

Background

To define the exact boundary of the intrathyroid and extrathyroid aspects of a gland when determining the extent of cancer invasion, we plan to clarify the definition of sizable vascular structures, which is one of the helpful histologic clues in determining a minimal extrathyroid extension. We hypothesized that arterial wall thicknesses in extrathyroid soft tissue would be significantly different from the arteries in the thyroid parenchyma.

Methods

Twenty cases of papillary carcinoma were selected. The numbers and wall thicknesses of the arteries and arterioles in intrathyroid and extrathyroid tissue were evaluated. The absence of nerve tissue in the thyroid gland was confirmed using the S-100 protein immunohistochemical stain.

Results

The comparison of the mean thicknesses of the total arteries between the extrathyroid and intrathyroid tissues in the retrospective study (26.88 µm vs. 15.07 µm, respectively) and the prospective study (35.24 µm vs. 16.52 µm, respectively) revealed significant differences (p=0.000). The greatest thickness of the intrathyroid arteries was 67.93 µm.

Conclusions

According to our results, the study showed that the extrathyroidal arteries were significantly thicker than the intrathyroidal arteries. We suggest that the sizable blood vessels of extrathyroidal arteries should be greater than 67.93 µm in thickness.

Citations

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Invasion in thyroid cancer: Controversies and best practices
Michiya Nishino, Jack Jacob
Seminars in Diagnostic Pathology.2020; 37(5): 219. CrossRef
MiR-221/222 promote migration and invasion, and inhibit autophagy and apoptosis by modulating ATG10 in aggressive papillary thyroid carcinoma
Hao Shen, Zaikai Lin, Haiyan Shi, Lingling Wu, Baojin Ma, Hong Li, Baobing Yin, Jun Tang, Hongjin Yu, Xiaoxing Yin
3 Biotech.2020;[Epub] CrossRef
Minimal extrathyroidal extension affects the prognosis of differentiated thyroid cancer: Is there a need for change in the AJCC classification system?
Zeming Liu, Yihui Huang, Sichao Chen, Di Hu, Min Wang, Ling Zhou, Wei Zhou, Danyang Chen, Haifeng Feng, Wei Wei, Chao Zhang, Wen Zeng, Liang Guo, Scott M. Langevin
PLOS ONE.2019; 14(6): e0218171. CrossRef
miR-199a-3p downregulation in thyroid tissues is associated with invasion and metastasis of papillary thyroid carcinoma
Chengbiao Liu, Meiling Xing, Liping Wang, Kejun Zhang
British Journal of Biomedical Science.2017; 74(2): 90. CrossRef
Clinicopathological Significance of Minimal Extrathyroid Extension in Solitary Papillary Thyroid Carcinomas
Chang Gok Woo, Chang Ohk Sung, Yun Mi Choi, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Won Bae Kim, Suck Joon Hong, Dong Eun Song
Annals of Surgical Oncology.2015; 22(S3): 728. CrossRef
Intraoperative Frozen Section for the Evaluation of Extrathyroidal Extension in Papillary Thyroid Cancer
Om Prakash Prajapati, A. K. Verma, M. Sabaretnam
World Journal of Surgery.2015; 39(7): 1855. CrossRef
Tumor Sprouting in Papillary Thyroid Carcinoma Is Correlated with Lymph Node Metastasis and Recurrence
Eunjung Lee, Wonkyung Jung, Jeong-Soo Woo, Jae Bok Lee, Bong Kyung Shin, Han Kyeom Kim, Aeree Kim, Baek-hui Kim
Korean Journal of Pathology.2014; 48(2): 117. CrossRef

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 Quantification, Expression of p53 Protein and MIB-1 in Colorectal Adenoma and Carcinoma.: Tae Jung Jang, Jung Ran Kim, Han Ik Bae; Korean J Pathol. 1997;31(1):40-50.

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Abstract PDF: Angiogenesis is a crucial step in tumor growth and progression. Scarce data is available on angiogensis in gastrointestinal tumors. We studied 16 normal colon, 44 adenomas and 29 carcinomas to evaluate angiogenesis in colorectal tumors and to assess the correlation among p53 protein, proliferative activity and other clinical prognostic parameters. Endothelial cells were immunostained with an anti-Factor VIII mAb; in each case three microscopic fields(x 200) were counted: average number of the three fields was defined as microvessel density (MVD). p53 protein expression was 45.5%(20/44) in adenomas, and 79.3%(23/29) in carcinomas (p<0.01). p53 protein expression of carcinomas was 57.1%(4/7) in diploid tumors, 100%(8/8) in aneuploid tumors (p=0.07), 100%(8/8) in well differentiated tumors, and 50%(2/4) in poorly differentiated tumors (p=0.09). MIB-1 score was 2.3+/-0.7(38) in adenomas, 3.4+/-0.5(29) in carcinomas (p<0.01). There was no significant correlation between p53 protein and MIB-1 score. MVD was 10.4+/-4.1(16) in the normal mucosa, 21.5+/-7.9(39) in the adenomas, 35.3+/-9.7(26) in carcinomas (normal versus adenomas, p<0.01; adenomas versus carcinomas, p<0.01). MVD was 25.8+/-5.4(2) in carcinomas confined to mucosa, and 36.1+/-9.6(24) in carcinomas with transmural invasion. The higher MIB-1 score was in carcinomas the more MVD increased but there was no statistical significance (r=0.38, p=0.055). MVD of carcinomas was not associated with nodal metastasis, p53 expression, and DNA ploidy. p53 protein and MIB-1 expression are useful methods for the evaluation of malignancy, and tumor angiogenesis is an early event in a colorectal tumor but MVD does not correlate with prognostic parameters except for the tumor depth.

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.

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.

Microvessel Density and Vascular Endothelial Growth Factor Expression in Invasive Breast Carcinomas.: Mi Yeong Jeon, Mee Young Sol, Kyung Sun Park, Hye Kyoung Yoon; Korean J Pathol. 2000;34(2):138-144.

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Abstract PDF: Angiogenesis is essential for tumor growth and metastasis, however, the prognostic value of neovascularization is undetermined. The aim of this study is to evaluate the prognostic significance of microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression in breast carcinomas. An immunohistochemical stains for CD 31 (DAKO) to estimate MVD and VEGF (Santa Cruz) were done on 40 cases of invasive breast carcinoma. MVD was calculated as an average count of vessels per 200 power field in the most vascularized areas. VEGF expression was interpreted according to staining intensity and number of positive cells. Mean MVD was 35, and MVD was not correlated with lymph node metastasis or histologic grade, but high MVD (mean MVD>35) showed an increasing tendency in cases with larger size, negative ER/PR, and positive cathepsin D. All of the cases showed VEGF expression, but VEGF expression was not correlated with tumor size, histologic grade, lymph node metastasis, ER/PR status, and cathepsin D expression. These results suggest that MVD and VEGF expressions are not reliable prognostic factors.

VEGF Expression and Microvessel Density in Oral Squamous Cell Carcinomas.: Ji Jun Lim, Sam Pyo Hong, Jae Il Lee, Seong Doo Hong, Chang Yun Lim; Korean J Pathol. 2000;34(3):190-198.

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Abstract PDF: Angiogenesis is an essential process in tumor growth and metastasis. VEGF has been considered a leading candidate inducing tumor angiogenesis. VEGF expression was significantly correlated with clinical stage, lymph node matastasis, and prognosis of cancers of various parts of body. However, little has been known about the correlation between VEGF expression and clinicopathologic parameters in oral squamous cell carcinoma. The aim of this study was to correlate VEGF expression with the clinicopathological parameters and microvessel density. Forty six oral squamous cell carcinomas were analyzed using immunohistochemical method with primary antibodies to VEGF and CD31. VEGF expression was detected in 33 (71.7%) of the 46 cases. The microvessel density was significantly correlated with VEGF expression (P=0.002). There was no correlation between microvessel density and tumour size, clinical stage, and lymph node metastasis, respectively. VEGF expression did not correlate with the histological grade of tumour differentiation, tumour size, and clinical stages. The VEGF-positive rate seemed to be higher in patients with cervical lymph nodal metastasis than in those without it, but it was not statistically significant. In conclusion, the overexpression of VEGF in the oral squamous cell carcinoma seemed to be associated with a more aggressive course of the disease. Further study is necessary to define the role of VEGF in oral squamous cell carcinoma.

Expression of Matrix Metalloproteinase and Tissue Inhibitor of Metallproteinase in Breast Carcinoma Related to Angiogenesis and Invasion.: Yoon Jung Choi, Woo Hee Jung, Hy De Lee, Kwang Gil Lee; Korean J Pathol. 2000;34(9):652-664.

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Abstract PDF: Among the enzymes which are responsible for basement membrane breakdown, matrix metalloproteinases (MMP) form a family of neutral proteases that are regulated at the levels of gene transcription, proenzyme activation by the cleavage of protein, and the inhibition of the active enzyme by tissue inhibitors of matrix metalloproteinases (TIMP). Recent reports have demonstrated that the expression of these proteolytic enzymes are elevated in several solid tumors and that it can be associated with invasiveness and poor prognosis. We examined the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 by immunohistochemistry in 160 cases of infiltrating ductal carcinoma. And we compared these data with the established prognostic parameters - tumor size, nodal status, clinical stage, hormonal receptor status, microvessel density, and TGF-beta1 expression in order to evaluate how MMP and TIMP expression are associated with breast cancer progression and prognosis. Microvessel density in invasive breast carcinoma was significantly correlated with tumor size and recurrence (p<0.05). The immunohistochemical expression of TGF-beta1 was significantly associated with tumor size, lymph node metastasis, and clinical stage (p<0.05). The microvessel density was significantly correlated with TGF-beta1 expression in more than 50% of tumor cells. The immunohistochemical expression of MMP-2 and MMP-9 were significantly correlated with nodal metastasis and absence of immunoreactivity for estrogen and progesterone receptors. The immunohistochemical expression of TIMP-1 was inversely correlated with clinical stage and microvessel density while that of TIMP-2 was inversely correlated with clinical stage (p<0.05). Small size of tumor, presence of progesterone receptor, highly differentiated histologic grade, and absence of immunoreactivity for MMP-9 were significantly associated with higher survival rate, but in multivariate analysis only tumor size and MMP-9 expression appeared to affect survival independently.

Case Report

Complete Hydatidiform Mole in Early Gestation: A Clinicopathologic Study of 51 Cases.: Kyu Rae Kim, Seung Koo Lee, Sun Young Jun, So Young Park; Korean J Pathol. 2002;36(2):93-99.

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Abstract PDF: BACKGROUND
With the widespread use of high resolution ultrasound in early pergnancy periods, poorly formed diagnostic features of complete hydatidiform mole (CHM) (which mimics normal or nonmolar gestation) often lead to a confusion fo CHM with partial mole, hydropic abortion or nonmolar chromosomal abnormalities.
METHODS
We studied the clinicopathologic finnings in 51 early CHM, evacuated before 12 weeks of gestation to characterize the early histologic changes.
RESULTS
Conventional diagnostic features were not uniformly identified; extensive cavitation was identified in 51.0%, trophoblastic hyperplasia in 49.1%, and avascular villi in 13.7%. The characteristic histologic features of early CHM were cellular and basophilic stroma (82.4%), bulbous projection with linear intervening clefts (76.5%), and apoptotic stromal cells (84.3%). In 86.3%, vascularized chorionic villi showed either primitive vascular network or clearly visible vascular lumen. Nonmetastatic persistent trophoblastic neoplasia developed in 35.3% and all were cured with single-agent or combination chemotherapy. Choriocarcinoma did not develop in any cases. The extent of trophoblastic proliferation at initial curettage han no prognostic value for clinical progression to persistent hydatidiform mole.
CONCLUSIONS
The fact that the histologic features of CHM in early gestation are often not as distinctive as those in later gestation should always be kept in mind in the diagnosis of conceptual products in early gestation.

Original Article

Light and Electron Microscopical Studies on the Stroma of Hydatidiform Mole.: Jong Tae Park, Sang Woo Juhng, Kyu Hyuk Cho; Korean J Pathol. 1987;21(4):240-248.

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Abstract PDF: Many investigators were interested in the pathogenesis and the relationship between microscopical features and clinical behavior of hydatidiform mole. Trophoblastic cells in the trophoblastic disease were intensively examined histologically, ultrastructurally, immunohistochemically, and with hormone assay method, etc. But ultrastructural study on the stroma of hydatidiform mole was scarcely reported. In this paper, hydatidiform mole was examined at light and electron microscopic levels, with emphasis on the stroma. The results were as follows: 1) Hydropic degeneration of H-mole is more severe in the center of stroma and is not related with the degree of trophoblastic proliferation. Hofbauer cell and vascular structure are extremely rarely observed in the periphery of stroma which has relatively preserved cellular components. 2) Basement membrane is sometimes separated from trophoblastic layer. Degenerated cells in the stroma contain vacuoles, autophagosomes, and lipid droplets. Collagen is abundant in the loose interstitium. Hofbauer cells have no lysosome or phagosome. Vascular lumen is patient and endothelial cells are degenerated. From the above results, H-mole may be produced due to abnormal changes of trophoblasts and stromal changes may be a secondary process, so called autolysis. Hofbauer cells are not engaged in the stromal degeneration and may be different from usual tissue macrophages.

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