J Pathol Transl Med.  2019 Sep;53(5):280-288. 10.4132/jptm.2019.05.13.

High Expression of Galectin-1, VEGF and Increased Microvessel Density Are Associated with MELF Pattern in Stage I-III Endometrioid Endometrial Adenocarcinoma

• Zinovkin D
• Achinovich SL
• Zubritskiy MG
• Whatmore J
• Pranjol MZ

• KMID: 2459576
• DOI: http://doi.org/10.4132/jptm.2019.05.13

Abstract

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 MELF-pattern 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.

Keyword

Endometrioid endometrial carcinoma; MELF pattern; Galectin-1; Microvessel density; VEGF

MeSH Terms

Adenocarcinoma*
Disease-Free Survival
Galectin 1*
Humans
Microvessels*
Prognosis
Vascular Endothelial Growth Factor A*
Galectin 1
Vascular Endothelial Growth Factor A

Figure

• 

  Fig. 1. Specific microcystic, elongated and fragmented pattern changes: endometrioid carcinoma showing eosinophilic glands with microcystic transformation embedded in fibromyxoid stroma and cancer cell complexes with some areas resembling vascular invasion.

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  Fig. 2. (A) A few positive glandular cells (microcystic, elongated and fragmented [MELF]–negative group). (B) All glandular cells positive for galectin-1 expression (MELF-positive group) in endometrioid carcinoma. (C) Positive local areas of cytoplasmic expression of vascular endothelial growth factor (VEGF; MELF-negative group). (D) Intense glandular and cytoplasmic (MELF-positive group) expression of VEGF in glands of the endometrioid carcinoma. Low (normal stroma) (E) and increased number of vessels (F) in fibromyxoid stroma situated around cancer cells forming gland without lumens.

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  Fig. 3. A correlation plot. Days, number of days of survival from surgical treatment to death or end of observation; MELF, microcystic, elongated and fragmented pattern; NoV, number of vessels per mm2 ; Gal-1, galectin-1 expression; AoV, area of vessels per mm2 ; Surv, survival (survival or death); VEGF, vascular endothelial growth factor expression.

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