title: B7-H4 (DD-O110) is overexpressed in high risk uterine endometrioid adenocarcinomas and inversely correlated with tumor T-cell infiltration.
abstract: OBJECTIVE
  B7-H4 (DD-O110), a member of the B7 family, negatively regulates T cell-mediated immune response. Previous studies have shown that B7-H4 is highly expressed in endometrioid 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 immunohistochemistry (IHC) in normal endometrium, endometrial 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 endometrial 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 tumors than in low risk tumors (p=0.001 and p=0.032, respectively). The proportion of B7-H4 positive tumor cells was inversely related to the number of CD3-positive and CD8-positive tumor-associated lymphocytes (TALs). There was a positive correlation between B7-H4 pattern 2 staining and both CD3-positive and CD8-positive tumor-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 number T cells associated with the tumor. These results suggest that B7-H4 overexpression may reflect a more aggressive biologic potential and may play a role in tumor immune surveillance mechanisms.
authors.affiliation: Department of Pathology, University of Colorado at Denver and Health Sciences Center, 12800 E.19th Ave. Aurora, CO 80010, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyatake
authors.forename: Barbara
authors.initials: B
authors.lastname: Tringler
authors.forename: Wenhui
authors.initials: W
authors.lastname: Liu
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Liu
authors.forename: Jackie
authors.initials: J
authors.lastname: Papkoff
authors.forename: Takayuki
authors.initials: T
authors.lastname: Enomoto
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Torkko
authors.forename: Donna L
authors.initials: DL
authors.lastname: Dehn
authors.forename: Ashanta
authors.initials: A
authors.lastname: Swisher
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Shroyer
mesh_terms: D017209:Apoptosis / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology*; D015153:Blotting, Western; D018269:Carcinoma, Endometrioid / Q000276:immunology* / Q000473:pathology; D004714:Endometrial Hyperplasia / Q000276:immunology / Q000473:pathology; D004717:Endometrium / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1
chemical_list: D018122:B7-1 Antigen; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human