Prognostic value of the co-expression of carbonic anhydrase IX and vascular endothelial growth factor in patients with clear cell renal cell carcinoma.

This study aimed to investigate whether the expression of carbonic anhydrase IX (CAIX) is associated with the expression of vascular endothelial growth factor (VEGF) and whether the co-expression of the two correlates with survival outcome in clear cell renal cell carcinoma (ccRCC). The expression of CAIX and VEGF was evaluated immunohistochemically in 122 paraffin-embedded ccRCC specimens. The clinical significance of these markers in relation to disease-specific survival (DSS) was analyzed. Patients with a low expression of CAIX had a significantly worse prognoses than those with a high expression (p=0.0005). Inversely, patients with a high expression of VEGF had a significantly worse prognoses than the patients with a low expression (p=0.0030). Furthermore, CAIX expression significantly stratified the DSS of patients with high-stage (p=0.0001), high-grade (p=0.0392), low-grade (p=0.0273), metastasis (p=0.0034), no metastasis (p=0.0303) and ECOG-PS=0 (p=0.0003). VEGF expression significantly predicted the survival of patients with low-grade (p=0.0003), high-stage (p=0.0401) and ECOG-PS=0 (p=0.0063). A multivariate Cox regression analysis showed that tumor stage (p=0.0054), metastasis (p=0.0193), ECOG-PS (p=0.0065) and CAIX expression (p=0.0001) were independent prognostic factors of DSS. Since CAIX and VEGF expression correlated inversely (p=0.0032), the prognostic value of the co-expression of CAIX-VEGF was evaluated. Multivariate analysis revealed that the co-expression was an independent prognostic factor of DSS (p=0.0002). In addition, the co-expression was able to stratify DSS into three risk groups: high-risk, intermediate-risk and low-risk (p<0.0001). In patients with ccRCC, CAIX and VEGF expression correlated inversely. Independent expression of CAIX and a co-expression of CAIX-VEGF were found to be independent predictors of DSS. Furthermore, the co-expression data for CAIX-VEGF provide more accurate prognostic information than the individual data. This information may be useful for survival prediction and risk stratification of patients with ccRCC.

Immunohistochemical analysis with multiple antibodies in search of prognostic markers for clear cell renal cell carcinoma.

OBJECTIVES: To simultaneously analyze multiple biologic markers to identify strong prognostic markers for disease-specific survival of patients with clear cell renal cell carcinoma (ccRCC). METHODS: The expression of Ki-67, p53, bcl-2, cyclin-D1, caveolin-1, vascular endothelial growth factor, and HER-2 was evaluated in 119 paraffin-embedded ccRCC specimens using immunohistochemistry. The clinical significance of these markers in relation to disease-specific survival was analyzed. RESULTS: On univariate analysis, high-level staining for Ki-67 (P <0.0001), p53 (P = 0.0029), vascular endothelial growth factor (P = 0.0062), and caveolin-1 (P = 0.0396) was associated with decreased survival, but high-level staining for bcl-2 (P <0.0001) and cyclin-D1 (P = 0.0002) was associated with increased survival. Only HER-2 expression was not related to survival (P = 0.1131). Multivariate analysis revealed the following independent predictors of disease-specific survival: expression of p53 (P = 0.0059) or bcl-2 (P = 0.0413) in all cases of ccRCC; expression of p53 (P = 0.0043) or bcl-2 (P = 0.0227) in cases of grade 1-2 disease; and expression of p53 (P = 0.0207) in cases with metastasis at surgery. CONCLUSIONS: Of the seven markers reviewed, p53 and bcl-2 were strong prognostic factors in all cases and in cases of grade 1-2 ccRCC. Only p53 attained independent prognostic significance in metastatic ccRCC. This information could prove useful in selecting markers to predict for survival and plan therapy for patients with ccRCC.