B7-H4 expression in ovarian serous carcinoma: a study of 306 cases

Hum Pathol. 2016 Nov;57:1-6. doi: 10.1016/j.humpath.2016.06.011. Epub 2016 Jun 24.

Abstract

The B7 family of immune costimulatory ligands is a group of cell surface proteins that bind to the surface receptors of lymphocytes to fine-tune immune responses. The aberrant expression of these proteins plays a key role in tumor immune evasion. Immunotherapy targeting certain B7 family members, including programmed death ligand 1, has proven quite effective in suppressing tumor growth. However, why such therapy works in only a subgroup of tumors is unclear. We hypothesized that other B7 family members, either alone or in concert with programmed death ligand 1, play a crucial role in tumor pathogenesis and progression. We therefore examined the expression of a newly discovered B7 family member, B7-H4, in 306 cases of ovarian serous carcinoma by immunohistochemistry. We found that 91% (267/293) of the high-grade ovarian serous carcinomas and 69% (9/13) of the low-grade ovarian serous carcinomas expressed B7-H4. The difference between B7-H4 expression in high-grade and low-grade ovarian serous carcinoma was statistically significant (P=.002). Moreover, B7-H4 protein expression in high-grade serous carcinoma was associated with tumor stage (P<.01) but not overall survival or disease-free survival. In conclusion, B7-H4 is frequently expressed in ovarian serous carcinomas, especially high-grade serous carcinomas, and may represent a novel immunotherapeutic target in this cancer.

Keywords: B7-H4; Fallopian tube; Immunohistochemistry; Immunotherapy; Ovarian cancer.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Carcinoma / immunology*
  • Carcinoma / mortality
  • Carcinoma / pathology
  • Carcinoma / therapy
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Immunotherapy / methods
  • Kaplan-Meier Estimate
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Grading
  • Neoplasm Staging
  • Neoplasms, Cystic, Mucinous, and Serous / immunology*
  • Neoplasms, Cystic, Mucinous, and Serous / mortality
  • Neoplasms, Cystic, Mucinous, and Serous / pathology
  • Neoplasms, Cystic, Mucinous, and Serous / therapy
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / therapy
  • Proportional Hazards Models
  • Time Factors
  • Treatment Outcome
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1 / analysis*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1
  • VTCN1 protein, human