VHL protein (pVHL) and Src expression in metastatic RCC.

457 Background: Rational therapeutic strategies are lacking for RCC with intact pVHL expression. We recently demonstrated that Src signaling output was elevated in RCC cells expressing pVHL (Suwaki Sci Transl Med 2011). We sought to prospectively identify and clinically characterize RCC patients according to tumor expression of pVHL and Src using an immunohistochemical (IHC) assay, including the association of pVHL and Src expression with response to targeted therapies. Methods: Metastatic RCC patients with available archival tumor tissue provided written informed consent. Primary and metastatic tumors were evaluated by IHC staining using the following scale: 0: absent; 1: weak; 2: moderate-strong. We scored the percent of tumor cells staining at these intensities, giving a total possible score of 200. Association of pVHL and Src score was determined using Spearman correlation coefficient. Time to treatment failure (TTF) > 300 days was used to stratify patients as treatment success versus failure. Logisti...