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T-Cell Immunoglobulin and Mucin Domain 1 (Tim1) as a Prognostic Factor Associated With Therapeutic Resistance in
Mio Yamaguchi-Tanaka1, Kiyoshi Takagi1, Mai Sawafuji1
1Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan, tohoku.ac.jp.
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.
Insights
T-cell immunoglobulin and mucin domain 1 (Tim1) expression in breast cancer correlates with poor prognosis and therapeutic resistance. Targeting Tim1 may improve treatment outcomes for breast cancer patients.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Therapeutic resistance is a significant challenge in breast cancer treatment, impacting endocrine and chemotherapy efficacy.
- T-cell immunoglobulin and mucin domain 1 (Tim1), a glycoprotein, shows aberrant expression in cancers, but its role in breast cancer and therapy resistance is unclear.
Purpose of the Study:
- To investigate the clinical significance of Tim1 expression in breast cancer.
- To analyze the association between Tim1 expression and clinicopathological parameters, treatment outcomes, and therapy resistance.
Main Methods:
- Immunohistochemistry was used to assess Tim1 expression in 116 breast carcinoma tissues.
- Correlation analysis was performed between Tim1 expression, clinicopathological factors, and patient outcomes following chemotherapy and endocrine therapy.
Main Results:
- Tim1 was expressed in breast carcinoma cells but not normal epithelium.
- Increased Tim1 expression correlated with advanced pathological T factor, lymph node metastasis, higher histological grade, and elevated Ki67 index.
- Tim1 expression was an independent adverse prognostic factor for disease-free survival and associated with recurrence risk, even after chemotherapy or endocrine therapy.
Conclusions:
- Tim1 expression is a significant adverse prognostic factor in breast cancer.
- Tim1 may represent a therapeutic target for overcoming treatment resistance in breast cancer patients.
