B7-H4 (DD-O110) is overexpressed in high risk uterine endometrioid adenocarcinomas and inversely correlated with tumor T-cell infiltration

Objectivc and inelhods. B7-H4 (DD-O110), a member of the 137 family, negatively regulates T cell-inediated immune response. Previous Studies have shown that B7-H4 is highly expressed in endoinctrioid ovarian cancers with relatively low levels of expression in normal ovary which was confirmed by Western blot. The present Study was designed to localize B7-H4 expression by inuilunohistochemistry (IHC) in normal endometrium, endorrietrial hyperplasia and uterine endometrioid adenocarcinoma. The pattern of B7-H4 localization was compared with the IHC detection of CD3 and CD8-positive T lymphocytes and CD14 positive macrophages to investigate the role of B7-H4 in the regulation of tumor immune Surveillance. B7-H4 expression was evaluated in apoptotic tumor cells. Results. The proportion and intensity of B7-H4 staining were increased in the progression from normal, hyperplastic and malignant endometrial glandular mucosa. B7-H4 showed a predominantly apical membranous staining (pattern 1) in normal and hyperplastic endonietrial epithelium but showed intense circumferential membranous and cytoplasmic staining (pattern 2) in a majority of endometrioid carcinoma cases (p=0.018). The proportion of B7-H4 positive tumor cells and staining intensity was also higher in high risk rumors than in low risk tumors (p=0.001 and p=0.032, respectively). The proportion of 137-1-14 positive tumor cells was inversely related to the number of CD3-positive and CD8-positive turnor-associated lymphocytes (TALs). There was a positive correlation between 137-H4 pattern 2 staining and both CD3-positive and CD8-positive tutnor-infiltrating lymphocytes (TILs) (p=0.039 and p=0.031, respectively). Conclusions. B7-H4 is overexpressed in hyperplastic and malignant endometrial epithelium and is correlated with the numberTcells associated with the unnor. These results suggest that B7-H4 overexpression may reflect a more aggressive biologic potential and may play a role in tumor immune surveillance mechanisms. (c) 2007 Elsevier Inc. All rights reserved.