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; ρ = 0.408). Corrected calcium level ≤ 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 ≥ 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.

Keywords: Renal cell carcinoma, Carbonic anhydrase IX, Cyclooxygenase-2, Vascular endothelial growth factor