Estrogen receptors expression in human bladder cancer and urogenital schistosomiasis.

Abstract

e16013 Background: Epidemiological and molecular findings suggest that estrogen may play a role in bladder carcinogenesis and in urogenital schistosomiasis (UGS). Methods: A comprehensive analysis of expression of estrogen receptors (ER) in urothelial carcinomas (UC), n = 80 from non-infected patients and UGS-related bladder carcinoma (BlaCa) n = 27 was undertaken. I n vitro, we evaluated the effect of estradiol (E2) and anti-estrogens on the survival of human BlaCa cells. In addition, molecular dynamics simulations are ongoing to assess the ability of estradiol-like metabolites produced by the Schistosoma haematobiumto bind ERs. Results: Tumor cell expression of ERα was found in 17.5% of the non-infected cases, and was associated with proliferative tumors (p = 0.004, ES = 0.326) and lower overall survival. Expression of ERα was also found in normal urothelium adjacent to the tumor and in tumor stromal cells, particularly in T2 and late stage tumors (p = 0.034, ES = 0.498and p = 0.037, ES = 0.357, respectively). In UGS-related BlaCa, 22% of tumor cells were ERα positive. Presence of parasite eggs was associated with higher ERα expression in cancer cells and adjacent urothelium (p = 0.038, ES = 0.399 and p = 0.020, ES = 0.600, respectively). ERβ was found in 91% of non-infected UC and 78% of the UGS-related tumors. ERβ was equally expressed across different tumor stages and grade but more intense in tumor cells than in urothelium of normal appearance and in non-infected than in UGS-related cases. In the latter group, staining intensity was increased in women and in samples with parasite eggs. Using 3 human BlaCa cell lines, HT1374, T24 and 5637, we observed that 5637 cells express ERα and can be stimulated by E2 and inhibited by the anti-estrogens (4OH-tamoxifen and ICI 182 780). T24 cells expressed ERα at very low levels and did not respond to E2, but were inhibited by anti-estrogens; HT1376 do not express ERα. ERβ mRNA was not detected in any of the cell lines. Conclusions: Our results document an association between expression of ERα and aggressive features. The potential of expression of ERs as a prognostic tool and as therapeutic target should be further investigated especially for tumors with aggressive profile and during UGS-related carcinogenesis.