J Pathol Transl Med.  2017 Sep;51(5):456-462. 10.4132/jptm.2017.07.19.

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

Affiliations
  • 1University Research Laboratory, Gomel State Medical University, Gomel, Belarus. zinovkin2012@gmail.com
  • 2University of Exeter Medical School, Institute of Biomedical and Clinical Science, Exeter, Devon, United Kingdom.
  • 3Laboratory of Endocrinology and Biochemistry, Institute of Radiobiology National Academy of Sciences, Gomel, Belarus.
  • 4Laboratory of Clinical Research, Republican Research Center for Radiation Medicine and Human Ecology, Gomel, Belarus.
  • 5Department of Oncology, Gomel State Medical University, Gomel, Belarus.

Abstract

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.

Keyword

Carcinoma, endometrioid; Vascular endothelial growth factor; Prognosis; MELF; Vessel density

MeSH Terms

Carcinoma, Endometrioid
Cohort Studies
Endometrial Neoplasms*
Female
Humans
Microvessels*
Prognosis
Republic of Belarus
Retrospective Studies
Risk Factors
ROC Curve
Survival Rate
Vascular Endothelial Growth Factor A*
Vascular Endothelial Growth Factor A

Figure

  • Fig. 1. (A) Stroma without fibroblastic reaction and tumor glands invading the myometrium. (B) MELF-pattern of the stroma with fibromyxoid reaction compressing the cancer glands. (C) Vessels in EA stroma with round lumen in group of patients with favorable outcome (arrows, CD34 immunostaining). (D) A large number of unusual vessels with dilated lumens in group of patients with unfavorable outcome (arrows, CD34 immunostaining). (E) Weak focal expression of VEGF in glands of EA, commonly detectable in patients with good outcome (VEGF immunostaining). (F) Diffuse strong expression of VEGF in glands of EA in cases of unfavorable outcome (VEGF immunostaining). MELF, microcystic, elongated, fragmented; EA, endometrioid adenocarcinoma; VEGF, vascular endothelial growth factor.

  • Fig. 2. Cumulative proportion survival. (A) MELF-pattern. (B) Number of vessels per 1 mm2. (C) Area of vessels per 1 mm2. (D) VEGF expression by tumor glands. MELF, microcystic, elongated, fragmented; VEGF, vascular endothelial growth factor.


Cited by  1 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.    doi: 10.4132/jptm.2019.05.13.


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