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

Gynecol Oncol. 2012 Jan;124(1):105-11. doi: 10.1016/j.ygyno.2011.09.012. Epub 2011 Oct 6.

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.

MeSH terms

  • Aged
  • B7 Antigens / biosynthesis*
  • B7 Antigens / immunology*
  • Blood Vessels / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Carcinoma, Endometrioid / blood supply
  • Carcinoma, Endometrioid / immunology*
  • Carcinoma, Endometrioid / pathology
  • Endometrial Hyperplasia / immunology
  • Endometrial Hyperplasia / pathology
  • Endometrial Neoplasms / blood supply
  • Endometrial Neoplasms / immunology*
  • Endometrial Neoplasms / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Retrospective Studies

Substances

  • B7 Antigens
  • CD276 protein, human