Correlation of c-Met Expression and Outcome in Patients With Renal Cell Carcinoma Treated With Sunitinib

Prognostic markers for treatment selection in metastatic renal cell carcinoma (mRCC) do not exist. This study evaluates c-Met expression in sunitinib-treated patients with mRCC, and elucidates its role as a possible marker for survival. c-Met expression was analyzed from 137 formalin-fixed paraffin-embedded tumor samples using a validated immunostaining protocol. High c-Met expression is associated with poor survival in patients with mRCC treated with sunitinib. Background: Treatment of patients with metastatic renal cell carcinoma (mRCC) has improved substantially since the introduction of targeted therapies, but no predictive biomarkers are available. The proto-oncogene c-Met is involved in tumor angiogenesis, development, and metastasis. The main objective was to evaluate c-Met expression in sunitinibtreated patients with mRCC, including patients with bone metastases. Methods: c-Met expression was analyzed from 137 formalin-fixed paraffin-embedded tumor samples using a validated immunostaining protocol. Results: Patients with low c-Met expression (n = 78) had longer progression-free survival (PFS) (median 14.3 vs. 6.5 months; P <.001) and overall survival (OS) (median 32.1 vs. 20.1 months; P =.049) than those with high expression. High c-Met expression was an independent predictor of unfavorable PFS in a Cox proportional hazards model adjusted for the Heng risk criteria (HR 1.60 [1.09-2.35]; P =.016). In a subgroup of patients with no bone metastases (n = 106), low cMet expression was associated with a both longer OS (unadjusted HR 0.63 [95% CI, 0.42-0.95]; P =.034) and PFS (unadjusted HR 0.47 [95% CI, 0.31-0.71]; P <.001). Conclusions: High c-Met expression was associated with poor survival in patients with mRCC treated with sunitinib. Interestingly, the prognostic role may vary based on the location of metastases. (C) 2017 Elsevier Inc. All rights reserved.