Importance of HLA-G expression and tumor infiltrating lymphocytes in molecular subtypes of breast cancer

Abstract

This study is aimed at investigating whether or not human leukocyte antigen-G (HLA-G) expression is associated with breast cancer molecular subtypes. HLA-G expression was immunohistochemically investigated in 104 patients with invasive ductal breast carcinoma, in which 56 were luminal A, 17 were luminal B, 19 were HER-2, and 12 were basal-like/normal breast-like subtype classified according to immunohistochemical staining results of ER, HER-2, CK5/6, and EGFR. Host immune response status was assessed by estimating the density of tumor infiltrating lymphocytes (TIL). For comparison, other biomarkers such as Ki67, p53 and VEGF were also investigated. Associations of these biomarkers and TIL with molecular subtypes were statistically analyzed. We found that there were more cases with high expressions of HLA-G in non-luminal than in luminal subtypes (P=0.035). In contrast, more cases with high density of TIL was found in luminal than in non-luminal subtypes (P=0.023). Compared to all the biomarkers studied, only HLA-G expression was found to be inversely associated with the density of TIL (P=0.004). Furthermore, patients with HLA-G(high)/TIL(low) status had a higher risk of recurrence than those with HLA-G(low)/TIL(high) status, regardless of the molecular subtypes. Therefore, a combination of the status of HLA-G and TIL could improve the prognostic prediction for patients with various molecular subtypes of breast cancer.