Expression of Myxovirus Resistance A (MxA) Is Associated with Tumor-Infiltrating Lymphocytes in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancers

Cancer Res Treat. 2017 Apr;49(2):313-321. doi: 10.4143/crt.2016.098. Epub 2016 Jul 7.

Abstract

Purpose: The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been determined in breast cancers. Interferons can affect T-cell activity through direct and indirect mechanisms. Myxovirus resistance A (MxA) is an excellent marker of interferon activity. Here,we evaluated TILs and MxA expression in human epidermal growth factor receptor 2 (HER2)-positive breast cancers.

Materials and methods: Ninety cases of hormone receptor (HR)+/HER2+ tumors and 78 cases of HR-/HER2+ tumors were included. The TILs level was assessed using hematoxylin and eosin-stained full face sections, and MxA expressionwas evaluated by immunohistochemistrywith a tissue microarray.

Results: MxA protein expression was significantly higher in tumors with high histologic grade (p=0.023) and high levels of TILs (p=0.002). High levels of TILs were correlated with high histological grade (p=0.001), negative lymphovascular invasion (p=0.007), negative lymph node metastasis (p=0.007), absence of HR expression (p < 0.001), abundant tertiary lymphoid structures (TLSs) around ductal carcinoma in situ (p=0.018), and abundant TLSs around the invasive component (p < 0.001). High levels of TILs were also associated with improved disease-free survival, particularly in HR-/HER2+ breast cancers. However, MxA was not a prognostic factor.

Conclusion: High expression of MxA in tumor cells was associated with high levels of TILs in HER2-positive breast cancers. Additionally, a high level of TILs was a prognostic factor for breast cancer, whereas the level of MxA expression had no prognostic value.

Keywords: Breast neoplasms; Myxovirus resistance proteins; Tumor-infiltrating lymphocytes.

MeSH terms

  • Adult
  • Biomarkers
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Middle Aged
  • Myxovirus Resistance Proteins / genetics
  • Myxovirus Resistance Proteins / metabolism*
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Tissue Array Analysis

Substances

  • Biomarkers
  • MX1 protein, human
  • Myxovirus Resistance Proteins
  • ERBB2 protein, human
  • Receptor, ErbB-2