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.