Prognostic effects and regulation of activin A, maspin, and the androgen receptor in upper urinary tract urothelial carcinoma

Background: Molecular mechanisms responsible for carcinogenesis in upper urinary tract urothelial carcinoma (UUTUC) are not yet clear. This study aimed to examine and correlate the subcellular localization of activin A, maspin, and the androgen receptor (AR) with demographic characteristics, pathological grade, and stage of UUTUC in a Taiwanese population, and to investigate the regulatory mechanisms for activin A, maspin, and AR. Material and Methods: Sections of stage I and II of UUTUCs from 93 patients were examined, with immunohistochemical detection of activin A, maspin, and AR. Patients were divided into four groups according to stage, grade, and disease-free interval (DFI). Pathologic characteristics and the subcellular localization of these markers were correlated with DFI. The urothelial carcinoma cell line HT1197 was stimulated with activin A at different time-points, and the mRNA expression of maspin before and after activin A stimulation was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Results: Expression of AR was observed to be stronger in stage II than in stage I of UUTUC. Expression of cytosolic activin A correlated with longer DFI for early-stage UUTUC (=0.048). Cellular and molecular localization examination revealed that a high level of activin A in the cytosol positively correlated with a high level of maspin in the cytosol (=0.038), and with increased AR expression in the cytosol (=0.044). By RT-PCR, mRNA expression of maspin was significantly induced after administering activin A to HT1197 cancer cells. Conclusion: Activin A can induce maspin expression in urothelial carcinoma cells. The expression level and localization of activin A, maspin and AR may be exploited and used as predictive markers for UUTUCs.