Immunoexpression of B7-H3 in endometrial cancer: relation to tumor T-cell infiltration and prognosis.

ABSTRACT

OBJECTIVE: B7-H3, a member of the B7 family of immune regulatory ligands regulates T cell-mediated peripheral immune response. The purpose of this study was to correlate the expression of B7-H3 and number of lymphocytes in patients with endometrial cancer. MATERIAL AND METHODS: A total of 107 patients with primary endometrial carcinoma (type I/endometrioid, n=81; type II, n=18) and endometrial hyperplasia (n=8) were investigated. Expression of B7-H3 in endometrial hyperplasia, endometrial carcinoma, and the endothelium of tumor-associated vasculature was assessed using immunohistochemistry from paraffin-embedded tissue blocks. Detection of CD8-positive tumor-infiltrating lymphocytes (TIL) and CD8-positive tumor-associated lymphocytes (TAL) was correlated with the expression of B7-H3. RESULTS: Patients with high grade tumors and patients with type II carcinomas expressed significantly more B7-H3 than low grade and endometrioid tumors (p=<0.0001 and p=0.0001, respectively). The expression of B7-H3 in the endothelium of identified vasculature in the tumor specimens showed similar results with strong relation to high grade tumors (p=0.001) and type II carcinomas (p=0.004). We found a significant correlation between B7-H3 expression on cancer cells and tumor T-cell infiltration (TIL) (p=0.017). In a univariate survival analysis, overexpression of B7-H3 in tumor cells was associated with shortened overall survival (p=0.005). CONCLUSIONS: B7-H3 is overexpressed on cancer cells and in the endothelium of tumor-associated vasculature in high grade tumors (G3) and type II carcinomas. B7-H3 expression on cancer cells is correlated with the number of T cells infiltrating the tumor. Endometrium tumor development and progression may be associated with downregulation of T-cell-mediated antitumor immunity through B7-H3.