MxA expression is associated with tumor-infiltrating lymphocytes and is a prognostic factor in triple-negative breast cancer

Breast Cancer Res Treat. 2016 Apr;156(3):597-606. doi: 10.1007/s10549-016-3786-z. Epub 2016 Apr 13.

Abstract

Interferons (IFNs) play an important role in tumor-immune system interactions. As one of the main mediators of IFNs, myxovirus resistance A (MxA) is upregulated in various cancers. However, the exact role of MxA in breast cancer is not fully understood. As part of the immune response to tumors, tumor-infiltrating lymphocytes (TILs) have prognostic significance in breast cancer. The aim of our present study was to examine the relationship between MxA and immune system components, including the amount of TILs and human leukocyte antigen (HLA) expression, in breast cancer. TILs, MxA expression, HLA intensity, and clinicopathological factors were retrospectively analyzed in 688 patients with primary breast cancer between 1993 and 1998 and in 705 patients with triple-negative breast cancer (TNBC) between 2004 and 2011. MxA expression was higher in TNBC tumors than in other subtypes. High MxA levels were associated with a higher histologic grade, abundant TILs, and stronger HLA-ABC expression in both the TNBC subtype within the consecutive breast cancer cohort and the validation TNBC cohort. MxA expression showed a significant positive correlation with TILs, the number of CD8(+) cells, and the number of CD69(+) cells in the validation TNBC cohort. High MxA levels and abundant TILs were found to be independent prognostic factors for disease-free survival in patients with TNBC. These results indicate that MxA expression is closely related to TILs in TNBC and, along with TILs, provides prognostic information after chemotherapy in patients with TNBC.

Keywords: Breast carcinoma; Human leukocyte antigen; Interferon; Myxovirus resistance A; Tumor-infiltrating lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Lectins, C-Type / metabolism
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology*
  • Myxovirus Resistance Proteins / metabolism*
  • Prognosis
  • Retrospective Studies
  • Tissue Array Analysis / methods*
  • Triple Negative Breast Neoplasms / immunology
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology*
  • Up-Regulation*

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Histocompatibility Antigens Class I
  • Lectins, C-Type
  • MX1 protein, human
  • Myxovirus Resistance Proteins