Abstract
Abstract Background: Recent studies have revealed aquaporins (AQPs) as targets for novel anti-tumor therapy, since they likely play a role in carcinogenesis, tumor progression, and invasion. Accordingly, we analyzed the prognostic impact of AQP3 expression and polymorphisms in a number of patients with early breast cancer (EBC). Patients and Methods: AQP3 expression was investigated on the basis of the immunohistochemistry of tissue microarray specimens from 447 EBC patients who underwent surgery between 2003 and 2008. We scored the staining intensity (0 through3) and percentage of positive tumor cells (0 through 4), and the staining score was defined as sum of these scores used to categorize the AQP3 expression as negative (0 through 2), weak (3 through 5), or strong (6 or more). For AQP3 polymorphisms, seven SNPs (rs10813981, rs34391490, rs591810, rs2227285, rs2228332, rs17553719, and rs3860987) were selected using in silico analysis and genotyped using the Sequenom MassARRAY. Results: A total of 180 (40.3%) of the patients were identified as AQP5-positive (staining score >2), including 86 (19.2%) cases of strong expression (stating score >5). In a univariate analysis, AQP3 expression was significantly associated with survival for the patients with HER2-overexpressing EBC. Moreover, a multivariate survival analysis revealed that AQP3 expression was an independent prognostic marker of disease-free survival (DFS: HR=3.137, 95%CI=1.079-9.125, p=0.036; Distant DFS: HR=2.784, 95%CI=0.921-8.414, p=0.070) for the HER2-overexpressing EBC patients. Meanwhile, none of selected AQP3 polymorphisms were related with AQP3 expression in tumor tissue nor survival in the current study. Conclusion: AQP3 expression in tumor tissue may be considered as a potential prognostic marker in patients with HER2-overexpressing EBC after curative surgery. Citation Format: Yee Soo Chae, Soo Jung Lee, Jeeyeon Lee, Jin Hyang Jung, Ho Yong Park. AQP3 expression predicts survival in patients with HER2-positive early breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-01-17.
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