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.