Abstract 3651: Foxp3 expression correlates with survival in urothelial carcinoma of the bladder

Abstract

Abstract Introduction and Objective The transcription factor Forkhead box p3 (Foxp3), originally described during the development of CD4+CD25+ T regulatory cells, has recently been implicated in divergent roles in human prostate, breast, pancreatic cancer, and melanoma. Here, we investigate the inducibility of Foxp3 in bladder cancer models and assess the prognostic role of Foxp3 in patients with bladder cancer. Methods Foxp3 expression in the human bladder cancer cell line SW780 was examined in in vitro cultures by flow cytometry and in in vivo subcutaneous implanted tumor models in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice by immunohistochemistry. Proliferation and invasion of SW780 cells in the absence of Foxp3 was performed by transfection of siRNA in vitro. Correlation of Foxp3 expression to urothelial carcinoma grade, stage, recurrence-free survival, and overall survival was examined in a human tumor microarray from a cohort of 280 patients by Cox proportional hazards regression and Kaplan-Meier analysis. Results Foxp3 expression correlates to higher cellular proliferation in vitro and in vivo. Knockdown of Foxp3 in SW780 cells resulted in decreased proliferation as well as invasion in vitro. Foxp3 expression increases with higher T stage, but not grade, as expression in adjacent normal bladder, Tis, Ta-1, T2-4, and lymph node metastasis was 1.2%, 3.8%, 15.2%, 26.5%, and 23.4% respectively, suggesting higher expression in muscle invasive and lymph node metastatic disease, but not carcinoma in situ. Using a cutoff of 10%, Foxp3 expression negatively correlates with survival following radical cystectomy with a median survival of 9.3 vs 2.8 years and a 10-year survival probability of 47% vs 27%. Conclusions This work implicates Foxp3 as novel transcription factor driving proliferation and tumor invasion in urothelial carcinoma. Expression of Foxp3 correlates with T stage and is a novel predictor of overall survival following radical cystectomy. Future studies will need to understand the mechanistic regulation of Foxp3 expression, as well examine Foxp3-mediated gene expression in urothelial carcinoma. Foxp3 expression may improve selection of patients to therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3651. doi:1538-7445.AM2012-3651