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

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.

Fig. 1.

Evaluation of tumor infiltrating lymphocytes (TILs) level by histology with hematoxylin and eosin–stained sections according to the recommendation by the International TILs Working Group and tertiary lymphoid structures. Interpreted as 50% (A, ×100) and 70% (B, ×200) of TILs and tertiary lymphoid structure (C, ×200), a lymph-node like lymphoid accumulation showing high endothelial venule (arrowheads).

Fig. 2.

Expression of myxovirus resistance A (MxA) by immunohistochemistry: negative staining (A, ×400), weak staining (B, ×400), moderate staining (C, ×400), and strong staining (D, ×400) for MxA.

Fig. 3.

Relationship between tumor infiltrating lymphocytes (TILs) level and disease-free survival in total human epidermal growth factor receptor 2 (HER2)–positive breast cancers (A), hormone receptor (HR)+/HER2+ breast cancers (B), and HR–/HER2+ breast cancers (C).