Immunolocalizations of VEGF, its receptors flt-1, KDR and TGF-beta's in epithelial ovarian tumors

Abstract

Objective: Angiogenesis is an essential factor for growth, differentiation, invasion and metastasis of tumors. In this study, we aimed to evaluate the immunolocalizations of vascular endothelial growth factor (VEGF), its receptors flt-1, KDR/flk-1, and transforming growth factor-beta's (TGF-beta) in epithelial ovarian tumors, utilizing indirect immunohistochemistry to understand the role of the angiogenic events in ovarian neoplasia.

Methods: Tissue blocks from 40 patients who had ovarian pathology (borderline serous-mucinous tumor and malignant serous-mucinous adenocarcinoma of the ovary) were included in this study. All formalin-fixed, paraffin-embedded tissue sections were stained with hematoxylin-eosin or primary antibodies against VEGF, flt-1, KDR/flk-1, TGF-beta1, TGF-beta2 and TGF-beta3 using the avidin-biotin-peroxidase method. H-SCORE, a semi-quantitative grading system, was used to compare immunohistochemical staining intensities.

Results: Positive VEGF immunoreactivity was concentrated in the epithelial and stromal parts of all the ovarian samples and the endothelial cells in the stroma were also stained. Increased immunoreactivity of VEGF was observed in malignant ovarian adenocarcinomas compared to the borderline tumors of the ovary. VEGF receptors, flt-1 and KDR/flk-1 immunoreactivities were detected not only in vascular endothelial cells, but also in tumor cells at malignant sites. Immunoreactivities of VEGF and its receptors were coexpressed in tumor cells of the ovarian carcinoma. While immunoreactivities of TGF-beta1 and TGF-beta2 were both overexpressed in malignant ovarian carcinomas, immunoreactivity of TGF-beta3 was still mild.

Conclusion: Our results suggest that overexpression of VEGF, its receptors flt-1, KDR/flk-1 and TGF-beta interaction may play an important role in the ovarian cancer biology, with potential effects on tumor growth and angiogenesis. New therapeutic strategies using VEGF and TGF-beta antagonists could obtain an additional approach to the treatment ovarian carcinoma by inhibiting angiogenesis.