BTN3A2 expression in epithelial ovarian cancer is associated with higher tumor infiltrating T cells and a better prognosis

PLoS One. 2012;7(6):e38541. doi: 10.1371/journal.pone.0038541. Epub 2012 Jun 7.

Abstract

BTN3A2/BT3.2 butyrophilin mRNA expression by tumoral cells was previously identified as a prognostic factor in a small cohort of high grade serous epithelial ovarian cancer (HG-EOC). Here, we evaluated the prognostic value of BT3.2 at the protein level in specimen from 199 HG-EOC patients. As the only known role of butyrophilin proteins is in immune regulation, we evaluated the association between BT3.2 expression and intratumoral infiltration of immune cells by immunohistochemistry with specific antibodies against BT3.2, CD3, CD4, CD8, CD20, CD68 and CD206. Epithelial BT3.2 expression was significantly associated with longer overall survival and lower risk of disease progression (HR=0.651, p=0.006 and HR=0.642, p=0.002, respectively) and significantly associated with a higher density of infiltrating T cells, particularly CD4+ cells (0.272, p<0.001). We also observed a strong association between the relative density of CD206+ cells, as evaluated by the ratio of intratumoral CD206+/CD68+ expression, and risk of disease progression (HR=1.355 p=0.044, respectively). In conclusion, BT3.2 protein is a potential prognostic biomarker for the identification of HG-EOC patients with better outcome. In contrast, high CD206+/CD68+ expression is associated with high risk of disease progression. While the role of BT3.2 is still unknown, our result suggest that BT3.2 expression by epithelial cells may modulates the intratumoral infiltration of immune cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Blotting, Western
  • Butyrophilins
  • Cell Line, Tumor
  • Cohort Studies
  • Female
  • Humans
  • Immunohistochemistry / statistics & numerical data
  • Kaplan-Meier Estimate
  • Lectins, C-Type / metabolism
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Mannose Receptor
  • Mannose-Binding Lectins / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasms, Glandular and Epithelial / genetics
  • Neoplasms, Glandular and Epithelial / metabolism*
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Proportional Hazards Models
  • Protein Isoforms / metabolism
  • Receptors, Cell Surface / metabolism
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology
  • Tissue Array Analysis / statistics & numerical data
  • Transfection

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • BTN3A2 protein, human
  • Butyrophilins
  • CD68 antigen, human
  • Lectins, C-Type
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Membrane Glycoproteins
  • Membrane Proteins
  • Protein Isoforms
  • Receptors, Cell Surface