Tumor associated endothelial expression of B7-H3 predicts survival in ovarian carcinomas

Xingxing Zang, Peggy S. Sullivan, Robert A. Soslow, Rebecca Waitz, Victor E. Reuter, Andrew Wilton, Howard T. Thaler, Manonmani Arul, Susan F. Slovin, Joyce Wei, David R. Spriggs, Jakob Dupont, James P. Allison

Research output: Contribution to journalArticle

123 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1104-1112
Number of pages9
JournalModern Pathology
Volume23
Issue number8
DOIs
StatePublished - Aug 1 2010

Keywords

  • B7
  • T cell
  • co-inhibition
  • co-stimulation
  • endothelium
  • ovarian cancer
  • serous carcinoma
  • tumor vasculature

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Zang, X., Sullivan, P. S., Soslow, R. A., Waitz, R., Reuter, V. E., Wilton, A., Thaler, H. T., Arul, M., Slovin, S. F., Wei, J., Spriggs, D. R., Dupont, J., & Allison, J. P. (2010). Tumor associated endothelial expression of B7-H3 predicts survival in ovarian carcinomas. Modern Pathology, 23(8), 1104-1112. https://doi.org/10.1038/modpathol.2010.95