Maspin overexpression correlates with increased expression of vascular endothelial growth factors A, C, and D in human ovarian carcinoma

The vascular endothelial growth factor (VEGF) family, including VEGFA, VEGFC, and VEGFD, plays an essential role in the angiogenesis of both pathologic and nonpathologic conditions. Maspin belongs to the serpin superfamily and has been identified as a tumor suppressor because it inhibits motility, invasion, and angiogenesis. Few studies have compared maspin with VEGF in ovarian carcinoma. Therefore, we investigated the expression and correlation of maspin, VEGFA, VEGFC, and VEGFD with the tumorigenesis of the ovary and clinicopathologic variables. Using immunohistochemistry, we examined maspin, VEGFA, VEGFC, and VEGFD expression in 60 ovarian carcinoma tissues (35 serous papillary carcinomas, 18 endometrioid carcinomas, and 7 primary ovarian mucinous carcinomas). Staining of cells was scored as + 2 if more than 50% of the cells were positive, as + I if less than 50% of the cells were positive, and as negative, if none of the cells stained positive. Overexpression of maspin, VEGFC, and VEGFD was significantly associated with high tumor grade (P<.001, P =.004, P<.001, respectively), clinical stage (P =.002, .01, and .001, respectively), the presence of ascites (P<.001, P =.03, and P =.001, respectively), and the presence of metastatic lymph nodes (P =.002, P<.001, and P<.001, respectively). Maspin was correlated with VEGFA (P =.01), VEGFC (P<.001), and VEGFD (P<.001). The VEGFA score was positively correlated with high tumor grade (P =.04), lymphovascular space invasion (LVSI) (P<.001), International Federation of Gynecology and Obstetrics (FIGO) stage (P =.009), maspin, VEGFC (P =.003), and VEGFD (P =.003), but it was not correlated with the presence of ascites and metastatic lymph nodes. Maspin, VEGFC, and VEGFD are expressed in ovarian tumors with a poor prognostic parameters, and seem to play a role in ovarian cancer angiogenesis, progression, and lymph node metastases. Our results indicate that in contrast to most other carcinomas, maspin expression is directly associated with the biological aggressiveness of ovarian carcinoma. These results may offer new insights regarding the role of maspin in ovarian cancer and might also affect the diagnosis and treatment strategies. (C) 2008 Elsevier GmbH. All rights reserved.