Molecular biomarkers for advanced renal cell carcinoma: implications for prognosis and therapy

Abstract

Objective: The aim of this study was to determine reliable predictive biomarkers for patients with metastatic renal cell carcinomas (RCCs) who had received cytokine therapy.

Methods: Tissue specimens were obtained from 62 patients with metastatic RCCs between 1995 and 2006. Paraffin wax embedded tissues were immunostained for carbonic anhydrase IX (CAIX), cyclooxygenase-2 (COX-2), and vascular endothelial growth factor (VEGF).

Results: Fifty-two specimens (84%) were assessed as clear cell type, with 5, 3, and 2 tumors showing sarcomatoid, papillary, and undifferentiated features, respectively. With a median 54 months of follow-up, 15/18 responding patients (83%) exhibited high CAIX staining compared with only 24/44 (55%) nonresponding patients (odds ratio, OR, 4.1; 95% confidence interval, CI 1.1-16.5, P = 0.04). There was a positive correlation between maximal COX-2 intensity and response for cytokine therapy (Spearman test P = 0.001; rho = 0.408). Corrected calcium level < or = 10 mg/dl (hazard ratio, HR, 0.1; 95% CI 0.15-0.28; P < 0.001), normal hemoglobin level (HR 0.30; 95% CI 0.15-0.50; P = 0.001), and COX-2 expression > or = 50% (HR 0.33; 95% CI 0.15-0.70; P = 0.008) were significant predictive factors of prolonged overall survival.

Conclusions: Thus, COX-2 and CAIX seem to be important predictors of outcome in patients with metastatic RCCs and might enhance the prognostic information obtained from pathology specimens.