Lower expression levels of the transforming growth factor beta receptor type II protein are associated with a less aggressive tumor phenotype and improved survival among patients with clear cell renal cell carcinoma.

Summary Loss of expression of the transforming growth factor β type II receptor (T β RII) has been implicated as an important event in renal carcinogenesis; however, its role as a potential prognostic factor remains poorly understood. Using archived tumor samples and long-term follow-up on a cohort of 280 clear cell renal cell carcinoma (ccRCC) patients treated with surgery from 1980 to 1998, we evaluated the association of T β RII expression and cancer-specific survival in both a univariate and multivariate setting. Low tumor expression of T β RII is associated with a less aggressive tumor phenotype at time of surgery. Moreover, those patients with lower levels of T β RII expression experience better cancer-specific survival than patients with higher levels of T β RII expression (log rank P = .034). Based on a Cox proportional hazard model adjusting for age, patients with tumors showing low (hazard ratio, 0.49; 95% confidence interval, 0.27-0.88) and moderate (hazard ratio, 0.7; 95% confidence interval, 0.40-1.23) T β RII expression are at decreased risk of RCC death compared with patients with tumors having high levels of T β RII expression. Adjustment for well-known pathologic predictors of RCC outcome attenuates the association of T β RII expression and ccRCC survival. Of interest, the association with T β RII expression appears more pronounced among those patients with tumors showing less aggressive phenotypes. Data from this investigation are the first to suggest that loss of T β RII expression is associated with improved ccRCC patient survival, especially among those patients with less aggressive disease profiles at time of surgery.