T-Cell Immunoglobulin and Mucin Domain 1 (Tim1) as a Prognostic Factor Associated With Therapeutic Resistance in Human Breast Carcinoma.

Background: Therapeutic resistance, including resistance to endocrine therapy in ER-positive tumors and to chemotherapy in aggressive subtypes, remains a major clinical challenge in breast cancer. T-cell immunoglobulin and mucin domain 1 (Tim1), a Type I transmembrane glycoprotein, has been reported to be aberrantly expressed in various cancer cells and contribute to tumor progression. However, its clinical significance in breast cancer and association with therapy resistance remain largely unclear. Methods: We investigated Tim1 expression by immunohistochemistry in 116 breast carcinoma tissues and analyzed its correlation with clinicopathological parameters and clinical outcomes according to chemotherapy and endocrine therapy status. Results: Tim1 immunoreactivity was detected in the cytoplasm and cell membranes of breast carcinoma cells but was negligible in the normal breast epithelium. Tim1 expression was significantly associated with pathological T factor, lymph node metastasis, histological grade, and Ki67 labeling index. Tim1 immunoreactivity was significantly correlated with an increased risk of recurrence, and multivariate analyses demonstrated Tim1 as an independent adverse prognostic factor for disease-free survival. In addition, Tim1 remained correlated with the risk of recurrence in patients who had received chemotherapy or endocrine therapy. Conclusions: Tim1 might be an important therapeutic target for improving therapy in breast cancer patients and could be a strong adverse prognostic factor associated with therapeutic resistance.