1073 RELEVANCE OF MTOR PATHWAY IN PROGNOSIS OF PATIENTS WITH UROTHELIAL CARCINOMA OF THE BLADDER

Abstract

INTRODUCTION AND OBJECTIVES: To investigate the role of mTOR signalling pathway on stage and outcome of patients with high grade and/or invasive bladder cancer. METHODS: Tissue microarrays were built from archival of high grade and mostly superficial bladder tumour specimens (n 143 with complete clinical data collected). Immunohistochemical staining was performed for Phosphatase and tensin homolog (Pten), phosphorylated (phos) Akt, phos-mTOR, phos-S6, phos-4EBP1 and p27. The markers were evaluated for pattern, percentage and intensity of staining (Hscore), and results correlated with clinicopathological characteristics and outcome. RESULTS: The median age at diagnosis of the patient cohort was 71 years (range: 38-96 years). The TNM stage group was distributed as pTa (44%), pT1 (49%) and pT2 (6%). After a median follow-up of 34 months, the disease recurrence, disease progression and overall death rates were 44%, 13%, and 11% respectively. The expression of p27 was significantly lower among pT2 compared to pTa and pT1 patients (p 0.03). The H-score of phos-mTOR was significantly correlated with p27 (p 0.003), pS6 (p 0.004) and 4EBP1 (p 0.001). In multivariate analysis, which included age, number of tumors, tumor size and stage, phos-S6 was an independent predictor of shorter recurrence-free (Hazard Ratio [HR]: 2.75, 95% Confidence Interval [CI]: 1.16-6.51). The expression of p27 was inversely correlated with recurrence-free survival (HR:0.37, 95% CI:0.18-0.88). None of the markers showed correlation with progression free survival and overall survival. CONCLUSIONS: Our results demonstrate that activation of mTOR pathway, as assessed by phosS6 might be used to provide prognostic information particularly as predictor of recurrence among patients with high-risk non-muscle invasive bladder cancer.