Molecular characterization of upper urinary tract tumours

To assess gene-expression patterns of BIRC5, FGFR3, IGF2, KRT20, UPK2, EBF1, CDH1, FXYD3, HTERT, TP53, AGR2, HER2 and VEGF, widely known markers of bladder urothelial carcinoma (UC) in upper tract UC, and to determine their value as prognostic factors of tumour progression and cancer-specific survival.

The study included 83 formalin-fixed paraffin-embedded tissue specimens (68 and 15 from patients with UTUC and controls, respectively) collected between 1990 and 2004. Thirteen bladder cancer-related genes were selected from previous reports and analysed by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) in all samples.

Six genes were over-expressed (BIRC5, FGFR3, KRT20, UPK2, FXYD3 and hTERT) and three under-expressed (AGR2, TP53 and VEGF) in the tumour group (P < 0.05). For four genes (IGF2, EBF1, CDH1 and HER2) there was no statistically significant difference between the tumour and control groups. Overall, 21 patients developed tumour progression and 13 died from UTUC after a mean follow-up of 35.24 months. The 5-year disease-free progression and cancer-specific survival rates were 65.8% and 72.9%, respectively. In a multivariate regression analysis, the independent predictive variable for tumour progression and cancer-specific survival was pathological stage (hazard ratio 3.60, P < 0.001; and 3.73, P < 0.005, respectively), but none of the studied genes were identified as prognostic factors of tumour progression or cancer-specific survival.

Our data suggest that bladder cancer and UTUC share some characteristics, but have differences in gene expression. None of BIRC5, FGFR3, IGF2, KRT20, UPK2, EBF1, CDH1, FXYD3, HTERT, TP53, AGR2, HER2 and VEGF were correlated either tumour progression or survival.