Association of Immunohistochemical Staining for p53 With Metastatic Progression and Poor Survival in Patients With Renal Cell Carcinoma

Abstract

Mutations of the p53 gene have been found in many types of human tumors. In some tumors, p53 gene mutations are associated with advanced disease and poor prognosis. There is wide variation in the reported incidence of p53 mutation in renal cell carcinoma, and its prognostic significance for this tumor is unknown. This retrospective immunohistochemical study was designed to examine associations between p53 immunostaining and histologic type, tumor grade, clinical behavior, and survival. Paraffin-embedded nephrectomy specimens collected from 1978 through 1986 from 175 patients were immunostained for p53 using the D07 monoclonal antibody. Positive staining for p53 has been linked to the accumulation of mutant p53 protein. Thirteen specimens of concurrent metastatic lesions were available from 11 primary cases. Clinical follow-up information was available on 164 patients. Immunostaining for p53 suggested the presence of p53 mutation in 49 (28%) of 175 renal tumors studied. Staining was associated with high tumor grade and stage but not with cell type or histologic pattern. Eleven (85%) of 13 metastatic lesions stained positively for p53, versus only four (36%) of the 11 paired primary tumors. Immunostaining for p53 was strongly associated with poor survival among patients without distant metastases at presentation. In this group, 10-year disease-specific survival was 78% for patients with nonstaining tumors versus 48% for those with p53-positive tumors (P < or = .003). There was an 87% 10-year disease-specific survival rate for patients with nonstaining Robson stage 1 tumors versus a 62% 10-year survival rate for patients with p53-positive Robson stage 1 tumors (P < .01). Multivariate analysis showed p53 immunoreactivity to be an independent predictor of survival for patients with nonmetastatic renal cell carcinoma, whereas tumor grade was not. Positive p53 immunostaining in renal cell carcinoma is associated with metastatic disease and poor survival in patients with early-stage disease. In renal cell carcinoma, mutations of the p53 gene may allow or contribute to the acquisition of metastatic potential.