Expression status and prognostic significance of mammalian target of rapamycin pathway members in urothelial carcinoma of urinary bladder after cystectomy

BACKGROUND: Bladder urothelial carcinoma has high rates of mortality and morbidity. Identifying novel molecular prognostic factors and targets of therapy is crucial. Mammalian target of rapamycin (mTOR) pathway plays a pivotal role in establishing cell shape, migration, and proliferation. METHODS: Tissue microarrays were constructed from 132 cystectomies (1994‐2002). Immunohistochemistry was performed for Pten, c‐myc, p27, phosphorylated (phos)Akt, phosS6, and 4E‐BP1. Markers were evaluated for pattern, percentage, and intensity of staining. RESULTS: Mean length of follow‐up was 62.6 months (range, 1‐182 months). Disease progression, overall survival (OS), and disease‐specific survival (DSS) rates were 42%, 60%, and 68%, respectively. Pten showed loss of expression in 35% of bladder urothelial carcinoma. All markers showed lower expression in invasive bladder urothelial carcinoma compared with benign urothelium with the exception of 4E‐BP1. Pten, p27, phosAkt, phosS6, and 4E‐BP1 expression correlated with pathologic stage (pathological stage; P