Expression of Mcl-1 Splicing Variants in Clear-Cell Renal Cancer and Their Correlation with Histopathological Parameters and Prognosis

Background/Aims: Altered expression of the Bcl-2 family member Mcl-1 has been linked to the progression and outcome of various malignancies, but its expression and potential prognostic value has yet not been investigated in clear-cell renal cell carcinomas (ccRCC). Methods: In this study, dual-colour real-time RT-PCR was used to quantify the expression of Mcl-1 splicing variants in malignant and paired normal renal tissue samples, obtained from 93 ccRCC patients (median follow-up: 45 months) undergoing radical nephrectomy. Results: Over-expression of the anti-apoptotic Mcl-1L variant in ccRCC occurred in nearly 60% of the paired samples (p = 0.004). Decreased expression, however, was related to poor tumour differentiation (p = 0.013) and independently predicted a higher risk for relapse (hazard rate 3.99; 95% CI 1.32-12.04; p = 0.014). Kaplan-Meier analyses revealed down-regulation of Mcl-1L in ccRCC to be associated with a markedly shortened recurrence-free and disease-specific survival, particularly in patients with locally advanced (p < 0.001 and p = 0.003) and poorly differentiated tumours (p = 0.004 and p = 0.011). Conclusion: These findings suggest Mcl-1L to provide a molecular parameter for outcome prediction in ccRCC patients, down-regulation indicating exceptionally aggressive tumour phenotypes. Copyright (C) 2009 S. Karger AG, Basel