Journal of Pathology and Translational Medicine

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

5,453 View
147 Download
4 Web of Science
5 Crossref

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

Citations to this article as recorded by

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
Endocervical Adenocarcinoma Showing Microcystic, Elongated, and Fragmented (MELF) Pattern of Stromal Invasion: A Single-Institutional Analysis of 10 Cases with Comprehensive Clinicopathological Analyses and Ki-67 Immunostaining
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
Role of adipocytokines in endometrial cancer progression
Ran Li, Fang Dong, Ling Zhang, Xiuqin Ni, Guozhi Lin
Frontiers in Pharmacology.2022;[Epub] CrossRef
Advances in Anti-Cancer Immunotherapy: Car-T Cell, Checkpoint Inhibitors, Dendritic Cell Vaccines, and Oncolytic Viruses, and Emerging Cellular and Molecular Targets
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

7,740 View
187 Download
21 Web of Science
18 Crossref

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

Citations to this article as recorded by

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

First
Prev
Page of 1
Next
Last

Search