P53, bcl-2, and Bax expression in renal cell carcinoma

Renal cell carcinomas often show a high degree of resistance to chemotherapy and radiation despite expressing normal function of the protein p53. The loss of control of apoptosis may also contribute to progression and resistance to treatment modalities and can be attributed to an interaction between p53 and the apoptotic regulators bcl-2 and Bax. To determine whether the expression of p53, bcl-2, or Bax could be correlated with outcome, we analyzed the expression pattern of these proteins in renal cell tumor samples.

We examined 28 patients with clear cell renal cell carcinomas along with 7 patients with papillary renal cell carcinomas and 4 with renal oncocytomas. All renal cell carcinomas were clinically localized Stage pT2 with tumor size ranging from 4.0 to 10.3 cm (mean 6.23). Immunohistochemistry was performed on all samples and correlated with markers of outcome, including tumor grade, metastasis, recurrence, and overall survival rate.

In all clear cell tumors, the detection level of p53 expression was below the sensitivity of the assay, consistent with the reported infrequent incidence of p53 mutations in renal cell cancers. bcl-2 expression showed a significant correlation (P = 0.018) with higher tumor grade but could not be significantly correlated with other parameters examined including tumor recurrence, metastasis, or survival rate. The expression of Bax could similarly be correlated with higher tumor grade but with none of the other parameters.

At the present time, the combination of both tumor grade and stage represents the best prognostic markers available. Adjunctive use of bcl-2 and Bax staining currently plays a minimal role in helping to further stratify patients at high risk for disease progression or recurrence.