Immunolocalizations of VEGF, its receptors flt-1, KDR and TGF-ß's in epithelial ovarian tumors
S. Inan1, S. Vatansever1, C. Celik-Ozenci2, M. Sanci3, N. Dicle4 and R. Demir2
1Celal Bayar University, Faculty of Medicine, Department of Histology & Embryology, Manisa, Turkey,2Akdeniz University, Faculty of Medicine, Department of Histology & Embryology, Antalya, Turkey,3Aegean Social Security Hospital, Department of Obstetrics & Gynecology, 4Department of Pathology, Izmir - Turkey
Offprint requests to: Sevinc Inan, M.D., Associate Prof. Celal Bayar University, Faculty of Medicine, Department of Histology & Embryology, Dekanlik Binasi, Uncubozkoy, Manisa, Turkey. e-mail: sevincinan@yahoo.com
Summary. 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-ß) 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-ß1, TGF-ß2 and TGF-ß3 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-ß1 and TGF-ß2 were both overexpressed in malignant ovarian carcinomas, immunoreactivity of TGF-ß3 was still mild.
Conclusion: Our results suggest that overexpression of VEGF, its receptors flt-1, KDR/flk-1 and TGF-ß 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-ß antagonists could obtain an additional approach to the treatment ovarian carcinoma by inhibiting angiogenesis. Histol Histopathol 21, 1055-1064 (2006)
Key words: Ovarian carcinoma, VEGF, flt-1, KDR, TGF-ß
DOI: 10.14670/HH-21.1055