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

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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

Citations to this article as recorded by

Association of Local and Distant Organ Metastases With MELF Pattern in Endometrial Cancer
Varol Gülseren, Ertuğrul Şen, Mehmet Dolanbay, Fulya Çağli, Nahit Topaloğlu, Figen Öztürk, Bülent Özçelik, Serdar Serin, Kemal Güngördük
International Journal of Gynecological Pathology.2024;[Epub] CrossRef
Tumour budding, MELF-pattern and tumour-infiltrating lymphocytes as possible pathomorphological parameters of the course of endometrioid adenocarcinoma of the uterine corpus
D. A. Zinovkin, I. V. Veyalkin, S. L. Achinovich, I. I. Slepokurova, Yu. A. Lyzikova, A. Farooq
Tumors of female reproductive system.2024; 20(2): 83. CrossRef
Determining the level of stromal and epithelial cells activity in normal and hyperplastic endometrium of late reproductive and perimenopausal women
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Journal of Medicine and Life.2023; 16(2): 210. CrossRef
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Biomedicines.2023; 11(11): 3026. CrossRef
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Xiqin Qi, Lun Zhu, Bei Zhang
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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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192 Download
23 Web of Science
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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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International Journal of Gynecological Pathology.2024;[Epub] CrossRef
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Biomarkers.2024; : 1. CrossRef
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Gynecologic Oncology.2022; 166(3): 530. CrossRef
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International Journal of Gynecological Pathology.2020; 39(5): 436. CrossRef
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Case Reports in Oncology.2020; 13(3): 1421. CrossRef
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