Alterations in SPARC and VEGF immunoreactivity in epithelial ovarian cancer

Objective. Secreted protein, acidic and rich in cysteine (SPARC), is a matr icellular protein that modulates cell adhesion and growth. It is thought to play a decisive role in tissue remodeling and angiogenesis, Alterations in SPARC expression have been observed in a variety of solid tumors; however, no consistent pattern of deregulation has been characterized. Vascular end othelial growth factor (VEGF) has emerged as an important regulator of tumo r neovascularization, Recent work has shown that SPARC modulates the mitoge nic activity of VEGF in normal endothelium. While its role in malignant tra nsformation remains elusive, SPARC may contribute to tumor propagation and invasion. This study examines the immunoreactivity of SPARC and VEGF associ ated with neoplastic transformation of the ovary. Methods. Immunostaining for VEGF and SPARC protein was performed on 62 arch ival specimens. Results, Fourteen normal ovaries and 48 ovarian carcinomas were evaluated. SPARC was detected in the stroma of 63% of ovarian carcinomas. In contrast, SPARC was observed in the stroma of only 29% of normal ovaries (P = 0.02). Furthermore, SPARC was limited in normal ovaries to premenopausal patients , juxtaposed either with vesiculated follicles or within the corpus luteum, VEGF was observed in 42% of ovarian carcinomas with immunoreactivity confi ned to tumor cells, The level of VEGF immunoreactivity was significantly hi gher in ovarian carcinoma compared to normal ovary epithelium (42 vs 7%, P = 0.02). Conclusions. Immunoreactivity of SPARC and VEGF is heightened in associatio n with ovarian carcinoma, with a distinct distribution of SPARC in the stro ma of neoplastic ovaries and VEGF within tumor cells. No obvious pattern of coincident SPARC and VEGF immunoreactivity was detected. These results ind icate the possibility of an aberration in the interaction that has been des cribed in normal endothelium between SPARC and VEGF in association with mal ignant transformation. (C) 2000 Academic Press.