SURVIVIN EXPRESSING CIRCULATING TUMOR CELLS IN NONMUSCHE INVASIVE BLADDER CANCER: A CELLECTION™ DYNABEADS ANALYSIS

INTRODUCTION AND OBJECTIVES: The prognosis of T1G3 bladder cancer is highly ariable and not predictable basing upon clinical and pathological prognostic factors. There is need for improvement in risk stratification in this population; understanding the molecular profile of individual patients could provide a more personalized and tailored treatment. Main objective was to evaluate the prognostic significance of Survivin in tumor tissues and that of Survivin expressing circulating tumor cells (CTCs) in T1G3 tumors. METHODS: 161 patients with T1G3 non muscle invasive bladder cancer (NMIBC), including CIS associated, were enrolled. Planned follow up was 24 mo. Survivin was evaluated by RT-PCR in tumoral tissues. CTCs were isolated from blood by CELLection™ dynabeads coated with the monoclonal antibody towards the human Epithelial Cell Adhesion Molecule. Cells were lysed and Dynabeads Oligo(dT) was used to capture poly A mRNA. cDNA was synthesised and analysed for the expression of CD45, CK8 and Survivin. The primary end point was disease free survival (DFS); the favourable group at 24 mo was defined as that without any clinical evidence of disease (NED); the unfavourable group was that with evidence of recurrent disease (RD) or progressive disease (PD). Tumour survivin expression and presence of CTC were correlated with DFS. Multivariate analysis was used to investigate whether the presence of CTC was an independent indicator of DFS. RESULTS: Survivin was found in about 50% of tumors. Survivin- patients showed a longer DFS than Survivin tumors (X2 6.222, p0.019). CTCs were found in 84/161 patients (52%); 96% of CTC were Survivin expressing. The difference in DFS between CTC - and CTC patients was statistically significant (X229.565; p0.001). CTC presence was found an independent prognostic factor of DFS (p0.001). CONCLUSIONS: To date, for bladder cancer, there is the lack of a realible marker able to predict the prognosis and with the capability to remark the biological bahaviour of hign-risk NMIBC. The presence of CTC is an independent prognostic factor in patients with T1G3 bladder cancer and in the future could be an important parameter to evaluate.