Prognostic Significance of Vascular Endothelial Growth Factor and Its Receptors in Endometrial Carcinoma

• Published in: Gynecologic oncology 2000-06, Vol.77 (3), p.413-418
• Main Authors: Yokoyama, Yoshihito, Sato, Shigemi, Futagami, Masayuki, Fukushi, Yoshiyuki, Sakamoto, Tomomi, Umemoto, Mika, Saito, Yoshiharu
• Format: Article
• Language: English
• Subjects: Adult; Biomarkers, Tumor - biosynthesis; Carcinoma - metabolism; Carcinoma - pathology; Endometrial Neoplasms - metabolism; Endometrial Neoplasms - pathology; Endothelial Growth Factors - biosynthesis; Endothelium, Vascular; Female; Humans; Immunohistochemistry; Lymphokines - biosynthesis; Neovascularization, Pathologic; Prognosis; Receptors, Growth Factor - biosynthesis; Survival Analysis; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1006/gyno.2000.5802

Objective. The aim of this study has been to evaluate the clinical significance of expression of VEGF and its receptors, Flt-1, KDR, and Flt-4, in endometrial carcinomas. Methods. Specimens of endometrial carcinomas from 86 patients were investigated immunohistochemically using respective specific antibodies. Additionally, samples from 14 patients with complex atypical endometrial hyperplasia (AEH) and 15 patients with normal endometria were also examined. Immunohistochemical assessment was classified as negative, weakly positive, and strongly positive according to staining intensity and the percentage of positive cells. Results. In positive cases, VEGF and its receptors were usually expressed homogeneously in the cytoplasms of cells in the endometrial carcimona, similar to the staining intensity of endothelial cells of stromal microvessels adjacent to carcinoma nests. The overall positive rates in the 86 carcinoma specimens were 66% for VEGF, 51% for Flt-1, 38% for KDR, and 57% for Flt-4. Their expressions in endometrial carcinoma tissues were high with significance or with borderline significance, compared to those in samples of complex AEH or normal endometria. Survival curves determined by the Kaplan–Meier method and univariate analysis showed VEGF, Flt-1, and Flt-4 overexpression to be related to poor prognosis of patients with endometrial carcinomas. However, multivariate analysis revealed that Flt-4 overexpression correlated independently with poor survival, similar to a value for myometrial invasion at one-half or more and that for retroperitoneal lymph node metastasis, whereas VEGF and Flt-1 overexpression did not. Conclusion. Flt-4 overexpression might be a promising prognostic indicator for survival of a patient with endometrial carcinoma.