Loss of expression of von Hippel-Lindau tumor suppressor protein associated with improved survival in patients with early-stage clear cell renal cell carcinoma

Objectives. To determine whether actual expression of the von Hippel-Lindau (VHL) protein product itself (pVHL) is associated with clear cell renal cell carcinoma (CC-RCC) survival. Recent data have suggested that somatic mutations of the VHL tumor suppressor gene are associated with better cancer-specific survival in patients with CC-RCC. Methods. Using a large, clinic-based cohort of 273 patients with CC-RCC, we tested the hypothesis that those patients with CC-RCC tumors lacking pVHL expression [pVHL(-)] will experience better cancer-specific survival than those patients with tumors that show pVHL expression [pVHL(+)]. Results. Using a Cox proportional hazard model adjusting for age, patients with pVHL(-) tumors were not at a decreased risk of CC-RCC death compared with patients with pVHL(+) tumors (hazard ratio 1.0, 95% confidence interval 0.7 to 1.5). Adjustment for the Mayo SSIGN score had little effect on the risk estimate (hazard ratio 0.8; 95% confidence interval 0.5 to 1.2). In our stratified analysis, we found evidence of an inverse association with loss of pVHL expression among those patients presenting with early-stage disease (hazard ratio 0.4; 95% confidence interval 0.2 to 0.8), even after adjustment for the Mayo SSIGN score. Conclusions. Although we report no overall association, the data from this investigation are consistent with earlier findings that suggest somatic VHL alteration is associated with better cancer-specific survival among those patients presenting with early-stage (pT1 and pT2) CC-RCC.