| Abstract: |
B7-H3 and B7x are members of the B7 family of immune regulatory ligands that are thought to attenuate peripheral immune responses through co-inhibition. Previous studies have correlated their overexpression with poor prognosis and decreased tumor-infiltrating lymphocytes in various carcinomas including uterine endometrioid carcinomas, and mounting evidence supports an immuno-inhibitory role in ovarian cancer prognosis. We sought to examine the expression of B7-H3 and B7x in 103 ovarian borderline tumors and carcinomas and study associations with clinical outcome. Using immunohistochemical tissue microarray analysis on tumor specimens, we found that 93 and 100% of these ovarian tumors express B7-H3 and B7x, respectively, with expression found predominantly on cell membranes and in cytoplasm. In contrast, only scattered B7-H3-and B7x-positive cells were detected in non-neoplastic ovarian tissues. B7-H3 was also expressed in the endothelium of tumor-associated vasculature in 44% of patients, including 78% of patients with high-stage tumors (FIGO stages III and IV), nearly all of which were high-grade serous carcinomas, and 26% of patients with low-stage tumors (FIGO stages I and II; P0.001), including borderline tumors. Analysis of cumulative survival time and recurrence incidence revealed that carcinomas with B7-H3-positive tumor vasculature were associated with a significantly shorter survival time (P0.02) and a higher incidence of recurrence (P0.03). The association between B7-H3-positive tumor vasculature and poor clinical outcome remained significant even when the analysis was limited to the high-stage subgroup. These results show that ovarian borderline tumors and carcinomas aberrantly express B7-H3 and B7x, and that B7-H3-positive tumor vasculature is associated with high-grade serous histological subtype, increased recurrence and reduced survival. B7-H3 expression in tumor vasculature may be a reflection of tumor aggressiveness and has diagnostic and immunotherapeutic implications in ovarian carcinomas. © 2010 USCAP, Inc. All rights reserved. |
| Keywords: |
adult; cancer survival; human tissue; aged; middle aged; survival rate; unclassified drug; major clinical study; cancer recurrence; advanced cancer; cancer incidence; neoplasm staging; adenocarcinoma; ovarian cancer; antigen expression; ovarian neoplasms; tumor markers, biological; endothelium cell; ovary; immunoenzyme techniques; survival time; endothelium, vascular; cell membrane; ovary carcinoma; cytoplasm; tissue array analysis; antigens, cd; endothelium; tumor vascularization; serous carcinoma; b7 antigen; fluorescent antibody technique, indirect; co-inhibition; co-stimulation; receptors, immunologic; b7 h3 antigen; t cell; antigens, cd80; b7; tumor vasculature
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