Epithelial and Tumor-associated Endothelial Expression of B7-H3 in Cervical Carcinoma

Abstract

B7-H3 is a transmembrane protein and a member of the B7 family of immune regulatory ligands. It exerts both inhibitory and stimulatory effects on the activation of T cells. We investigated the expression of B7-H3 in invasive squamous cell carcinoma (ISCC) of the uterine cervix by immunohistochemistry, and aimed to determine whether expression of this factor is involved in the progression of the morphologic spectrum from normal cervical epithelia to cervical intraepithelial neoplasia and cervical ISCC. In addition, we sought to examine the relation of B7-H3 to the abundance of tumor-infiltrating and tumor-associated CD8(+) lymphocytes and to the evidence of phosphohistone H3, which is a core histone protein detected during mitosis. B7-H3 immunostaining was scored with regard to quantity and intensity of positively stained cells, and was noted in membranous and cytoplasmic patterns in epithelial cells and on endothelia of stromal blood vessels. Compared with those in intraepithelial neoplasias, immunoscores were significantly increased in ISCC (P<0.0001 for epithelial and endothelial expression, respectively). High scoring was associated with International Federation of Gynecology and Obstetrics stages IB and higher. Immunoscores of epithelial and endothelial B7-H3 expression were correlated significantly (P=0.0358). Epithelial and endothelial expression of B7-H3 was inversely related with CD8(+) tumor-infiltrating lymphocyte (P<0.0001). Moderate/strong B7-H3 epithelial as well as endothelial expression was mutually increased with intermediate/strong phosphohistone H3 scores (P=0.0396 and P=0.0483, respectively). There was no statistical relation with survival; however, no patient with negative scoring died of her tumor. Our results indicate that B7-H3 expression in cervical ISCC may play an important role in overcoming CD8(+) T-cell immunoregulation to acquire aggressive growth.