The expression of epidermal growth factor receptor 2 and its relationship with tumor-infiltrating lymphocytes and clinical pathological features in breast cancer patients.

Abstract

Breast cancer (BC) is a common malignant tumor with a frequent occurrence in women, and its occurrence and progression are influenced by various factors. This work aimed to investigate the expression of human epidermal growth factor receptor-2 (HER-2) in BC and its relationship with tumor-infiltrating lymphocytes (TILs) and the clinical pathological features of BC patients. Data from 470 BC patients were collected, and TIL levels were assessed. Immunohistochemistry (IHC) was performed to further analyze the relationship between TILs and clinical pathological parameters, as well as the expression of CD8 and HER-2. Immunohistochemical results revealed that the HER-2-positive expression rate was 28.72% (135/470), and its expression intensity significantly increased with higher histological grades (low grade: 15.2%, moderate grade: 28.5%, high grade: 42.6%, P < 0.05). CD8-positive cells were predominantly located in the tumor stroma, with a positive rate of 56.38% (265/470). Moreover, the positive expression intensity in the high TIL level group was significantly higher than in the low TIL level group (high TIL group: 78.9%, low TIL group: 35.4%, P < 0.05). The statistical results indicated that 37.45% (176/470) of cases exhibited no or low TIL levels, 42.34% (199/470) showed moderate TIL levels, and 20.21% (95/470) presented high TIL levels. TIL levels were significantly associated with histological grade of BC (percentage of high-grade cases in the high TIL group: 65.3%, in the low TIL group: 22.1%, P < 0.05), Ki-67 index (high TIL group: 45.2% ± 12.3%, low TIL group: 25.6% ± 10.8%, P < 0.05), vascular tumor embolism (VTE) (VTE-positive rate in the high TIL group: 38.9%, in the low TIL group: 12.4%, P < 0.05), lymph node metastasis (LNM) (LNM-positive rate in the high TIL group: 52.6%, in the low TIL group: 28.4%, P < 0.05), and estrogen receptor (ER) expression (ER-negative rate in the high TIL group: 68.4%, in the low TIL group: 32.1%, P < 0.05). Spearman correlation analysis revealed a positive correlation between TILs and HER-2 (r = 0.149, P = 0.002), as well as CD8 (r = 0.593, P = 0.001). Analysis of the GEPIA database showed that patients with high HER-2 expression had significantly lower disease-free survival (DFS) compared to those with low expression (hazard ratio [HR] = 1.45, P = 0.003), while patients with high CD8 expression exhibited significantly higher DFS than those with low expression (HR = 0.72, P = 0.001). In HER-2-positive BC patients, TIL levels were positively correlated with HER-2 and CD8 expression (high HER-2 expression group: TIL high expression rate 48.6%, low HER-2 expression group: TIL high expression rate 15.2%, P < 0.05). TIL levels in HER-2-positive BC patients were positively correlated with both HER-2 and CD8 expression. TIL levels were closely related to the prognosis of BC patients, which may provide a theoretical basis for precision treatment in BC.