Overexpression of aquaporin-1 in non-small cell lung cancer.

Abstract

e21078 Background: In 2003, Peter Agre and Roderick MacKinnon were awarded the Nobel Prize in chemistry for their pioneering discoveries concerning the aquaporins. The aquaporins are channel proteins that regulate water transport across cell membranes. Since most tumors exhibit high vascular permeability and interstitial fluid pressure, a possible role of the aquaporins in tumor development, growth, and spread has been suggested. Studies on the function of aquaporin-1 (AQP-1), which is located in the alveolar epithelial cells of the lung, may provide insights leading to the design of novel therapeutic approaches for lung cancer. The purpose of this study was to investigate the expression of AQP-1 in various types of lung cancers (52 adenocarcinomas, 12 bronchoalveolar carcinomas, 25 squamous cell carcinomas) by immunohistochemical staining. Methods: Tissue microarrays (TMAs) of lung cancers were stained with AQP-1 antibodies to identify expression of AQP-1 in non-small cell lung cancer. The immunohistochemical results found for each tissue sample were then correlated with the respective patient's clinical features, including their age, gender, stage, histology, and grade. Results: Results of this study demonstrate a significant correlation between AQP-1 expression and histological subtypes of lung cancer. AQP-1 was overexpressed in 69% (36 of 52) and 67% (8 of 12) of adenocarcinomas and bronchoalveolar carcinomas, respectively, compared to only 36% (9 of 25) of squamous cell carcinomas (p = 0.0049). Only 33% of normal lung tissue overexpressed AQP-1, compared to 60% of all lung cancer tissue studied (p = 0.1941). There was no correlation between AQP-1 stain intensity and lung cancer grade or stage. Conclusions: Based on tumor-specific overexpression, it is proposed that increased levels of AQP-1 may play a role in tumorigenesis. While more regarding the molecular composition of AQP-1 related to tumorigenesis remains to be elucidated, the protein has the potential to become a targeted therapy and the discovery of AQP-1 inhibitors could have biologic and clinical implications in lung cancer. No significant financial relationships to disclose.