Abstract
The calcium-activated chloride channel Ano1 (TMEM16A) is overexpressed in many tumors. Although Ano1 overexpression is found in breast cancer due to 11q13 amplification, it remains unclear whether signaling pathways are involved in Ano1 overexpression during breast cancer tumorigenesis in vivo. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) have been known to contribute to breast cancer progression. It is unclear whether Ano1 is associated with clinical outcomes in breast cancer patients with different ER, PR and HER2 status. In the present study, we investigated the Ano1 expression in 431 patients with invasive ductal breast carcinoma and 46 patients with fibroadenoma, using immunohistochemistry, and analyzed the association between Ano1 expression and clinical characteristics and outcomes of breast cancer patients with different ER, PR, and HER2 status. Ano1 was overexpressed in breast cancer compared with fibroadenoma. Ano1 was significantly more associated with breast cancer with the lower clinical stage (stage I or II), or triple-negative status. Mostly importantly, Ano1 overexpression was associated with good prognosis in patients with the PR-positive or HER2-negative status, and in patients following tamoxifen treatment. Multivariate Cox regression analysis showed that Ano1 overexpression was a prognostic factor for longer overall survival in PR-positive or HER2-negative patients, and a predictive factor for longer overall survival in patients following tamoxifen treatment. Our findings suggest that Ano1 may be a potential marker for good prognosis in PR-positive or HER2-negative patients following tamoxifen treatment. The PR and HER2 status defines a subtype of breast cancer in which Ano1 overexpression is associated with good prognosis following tamoxifen treatment.
Highlights
Anoctamin 1 (Ano1, TMEM16A) is one of 10 members in the Ano family that are involved in a variety of functions including ion transport and phospholipid scrambling [1]
Consistent with these studies, we found that Ano1 was overexpressed in breast cancer compared with fibroadenoma
The findings that Ano1 is overexpressed in breast cancer compared with benign fibroadenoma and tumor-adjacent normal breast tissues suggest that Ano1 overexpression may contribute to malignant transformation of mammary epithelial cells into breast cancer
Summary
Anoctamin 1 (Ano, TMEM16A) is one of 10 members in the Ano family that are involved in a variety of functions including ion transport and phospholipid scrambling [1]. Attention has been focused on the role of Ano in cancers [11,12,13,14,15]. Before it was identified as a CaCC in 2008 [6,16,17], Ano ( known as ORAOV2, DOG1, TAOS2, and FLJ10261) is found to be overexpressed in many cancers such as esophageal squamous cell cancer, gastrointestinal stromal tumor, and head and neck squamous cell carcinoma [18,19,20,21]. Ano overexpression has been found to be due to amplification of the corresponding chromosomal region in 11q13 [11,15,24,25], and correlates with poor prognosis in patients with breast cancer and head and neck squamous cell carcinoma [15,25]
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