Vascular endothelial growth factor expression in serous ovarian carcinoma:: relationship with topoisomerase IIα and prognosis

Objective. This study investigated the expression of vascular endothelial growth factor (VEGF) and topoisomerase IIalpha (TPIIalpha) in a cohort of serous ovarian carcinomas by immunohistochemistry with regard to outcome and clinicopathologic variables. Methods. Formalin-fixed, paraffin-embedded archival tissue sections of 10 benign serous cystadenomas and 41 serous ovarian carcinomas were immunostained with antibodies to VEGF and TPIIalpha. Immunostaining for VEGF was scored with regard to quantity and intensity of positively stained cells as weak, focal strong, and diffuse strong. TPIIalpha labeling indices (LI) were quantitated as the percentage of positively stained nuclei in 1000 tumor cells. Results. VEGF expression was weak or negative in serous cystadenomas. In contrast, focal or diffuse strong immunostaining was observed in 21 cases (51%) of serous carcinomas. VEGF immunoreactivity was positively related with TPIIalpha LI (P=0.0055), adverse outcome (P=0.0052), high International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.0158), and high tumor grade (P=0.0303). TPIIalpha LI increased with FIGO stage (P=0.0076) as well as tumor grade (P=0.0034) and indicated poor prognosis (P=0.0182). Conclusions. VEGF immunoreactivity is related with TPIIalpha LI and prognostically relevant. Expression of VEGF protein and TPIIalpha may serve as markers of aggressive tumor behavior in serous adenocarcinomas. (C) 2004 Elsevier Inc. All rights reserved.