The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors

Abstract

B7-H1 molecule increases the apoptosis of tumor-reactive T lymphocytes and reduces their immunogenicity. Breast cancer is the second most common cause of mortality after lung cancer. Direct evidence linking B7-H1 with cancer has been shown in several malignancies; however, its expression in breast cancer has not been investigated. We used immunohistochemistry to investigate the expression of the B7-H1 molecule in 44 breast cancer specimens and to study its correlation with patients' clinicopathological parameters. The expression of B7-H1 was shown in 22 of 44 patients and was not restricted to the tumor epithelium (15 of 44, 34% in tumor cells), but was also expressed by tumor-infiltrating lymphocytes (TIL; 18 of 44, 41%). Interestingly, intratumor expression of B7-H1 was significantly associated with histologic grade III-negative (P = .012), estrogen receptor-negative (P = .036), and progesterone receptor-negative (P = .040) patients. In addition, the expression of B7-H1 in TIL was associated with large tumor size (P = .042), histologic grade III (P = .015), positivity of Her2/neu status (P = .019), and severe tumor lymphocyte infiltration (P = .001). Taken together, these data suggest that B7-H1 may be an important risk factor in breast cancer patients and may represent a potential immunotherapeutic target using monoclonal antibody against the B7-H1 molecule.

Figure 1

Immunocytochemical staining of B7-H1-negative MCF-7 (A) and B7-H1-positive MDA-MB-231 (B) breast cancer cell lines confirm their phenotype, as shown by FACS analysis. Photomicrographs, x400 magnification. Representative immunohistochemical staining in a B7-H1-positive breast cancer patient is also presented. (C) A section from adjacent normal breast lobules (N) showing a negative reaction to B7-H1 antibody. (D) A section from the tumor tissue side (T) showing a positive reaction to B7-H1 antibody. Note that the red-orange single stain represents B7-H1 expression. The localization of B7-H1 to epithelial tissues in the tumor section (T) is presented by the double staining (arrow in F; blackish dark color) of pan-Cytokeratin (single red color) and B7-H1 (single brown color). (E) Low magnification, x100. (F) High magnification, x540.

Figure 2

Representative immunohistochemical staining shows the expression of B7-H1 by TIL. The expression of B7-H1 by TIL is shown using double staining (arrow in B; blackish dark color) for B7-H1 (single brown color) and CD3 (single red color), and using a nuclear (blue color) counterstain. (A) Low magnification, x130. (B) High magnification, x540. The subsets of TIL expressing B7-H1 were identified using double staining (arrow in D) for B7-H1 (single brown color) and CD4 (single red color). (C) Low magnification, x130. (D) High magnification, x540. The double staining of B7-H1 and CD8 molecules is shown. (E) Low magnification, x130. (F) High magnification, x540.