Differential Expression of Aquaporins in Cervical Precursor Lesions and Invasive Cervical Cancer

Objective: Aquaporins (AQPs) are highly expressed in tumor cells of different origins, particularly the aggressive tumors. The aim of this study was to investigate the expression of AQP isoforms during progression of squamous cervical cancer (SCC) and explore their associations with clinicopathologic variables of SCC. Methods: Expression of AQP isoforms (1, 3, 4, 5, and 8) was detected by immunohistochemistry in 47 SCCs, 37 cervical intraepithelial neoplasia (CIN), and 16 normal cervical tissues. Specific expression of AQP protein in SCC was detected by Western blot. Double immunohistochemistry was used to examine whether AQPs and vascular endothelial growth factor (VEGF) are coexpressed in SCC. Results: Aquaporin 1 showed higher positivity rate in CIN than in SCC and normal cervical tissues (P < .05). The expression intensity of AQP3, 4, 5, and 8 was higher in SCC than that in normal cervical tissues, respectively (P < .05). The expression of AQP3 and 8 was higher in SCC than that in CIN, respectively (P < .05). The AQP4 expression was higher in CIN than in normal cervical tissues (P < .05). The expression of AQP3 in CIN III was higher than that in CIN I and II (P < .05). There was a significant increase in the expression of AQP1 in stage I than that in stage II (P < .05). Aquaporin 3 showed lower positivity in moderately and well-differentiated tumors compared to that in poorly differentiated tumors (P < .05). Finally, double immunohistochemistry illustrated that AQP1/AQP3/AQP8 and VEGF were coexpressed in SCC. Conclusions: Different AQP isoforms display specific expression patterns in normal cervical, CIN, and SCC tissues. This and the significant association with the clinicopathologic variables of SCC suggest that AQP isoforms might play different roles in the development of cervical cancer.