Implications of androgen receptor and FUS expression on tumor progression in urothelial carcinoma

Abstract

Androgen receptor (AR) interact with many pathways involved in bladder cancer development and progression. FUS (fused in liposarcoma), a multifunctional protein essential for different cellular processes, has been demonstrated as a key link between androgen receptor signaling and cell-cycle progression in prostate cancer but has not been examined in urothelial carcinoma (UC) despite an intimate association between prostate and bladder carcinogenesis. Aim. to examine the immunohistochemical expression of AR and FUS in urothelial carcinoma in relation to prognostic parameters and to extrapolate any possible link between the expression of both markers and tumor progression. Study design. Retrospective study using immunohistochemical staining for AR and FUS on (88) cases of urothelial carcinoma. Results. AR shows statistically significant relations with late tumor stage, high tumor grade, and nonpapillary tumor pattern. On the other hand, FUS expression correlates with early tumor stage, low tumor grade and papillary pattern. An inverse relation is found between AR and FUS expression (p=0.001). Cases with high AR IHC expression show statistically significant shorter OS, RFS and PFS compared to cases with low AR expression. Cases with high FUS IHC expression reveal statistically significant longer OS, RFS and PFS compared to cases with low FUS expression. Conclusion. FUS expression is associated with favorable prognostic parameters of UC. A possible interaction is suggested between FUS and AR pathways involved in urothelial cancer progression. Manipulating FUS levels and androgen deprivation therapy can provide new promising targets for treatment trials.