Elevated content of p53 protein in the absence of p53 gene mutations as a possible prognostic marker for human renal cell tumors

Abstract

p53 tumour suppressor gene expression was estimated immunohistochemically using DO-1 monoclonal antibody (recognising both wild-type and mutant p53 in 88 human renal tumours. Single strand conformation polymorphism (SSCP) analysis of possible mutations within exons 4-8 of the p53 gene was performed in 29 of the tumours (mostly immunostaining-positive cases). Obviously elevated p53 content was detected with DO-1 antibody in chromophobic cell carcinomas and most clear/chromophilic cell tumours (in chromophilic cell populations). In contrast, clear cell carcinomas demonstrated either complete absence of p53 expression or the presence of single immunopositive nuclei. Oncocytomas were completely negative. Additional immunostaining of the positive samples with mutant p53-specific Pab240 monoclonal antibody failed to detect immunopositive material. No p53 mutation was found in any of the samples analysed by SSCP. Our results suggest that the elevated p53 content in human renal cell carcinomas does not result from gene mutation and the p53 gene alterations are probably not an important mechanism in the development of human renal cell carcinomas. Accumulation of the wild-type p53 protein may be a useful prognostic marker indicating neoplastic progression malignancy.

p53 protein expression but not mdm-2 protein expression is associated with rapid tumor cell proliferation and prognosis in renal cell carcinoma

“…A nuclear p53 overexpression was found in 16% of 50 nonpapillary pT3 RCCs. This is similar to the rate found in several other studies (range from 11% to 33%) [4,[21][22][23]. Overexpression of the p53 protein is often caused by missense mutations of thep53 gene, since p53 gene mutations lead to stabilization of the protein which can then be detected by immunohistochemistry.…”

“…Overexpression of the p53 protein is often caused by missense mutations of thep53 gene, since p53 gene mutations lead to stabilization of the protein which can then be detected by immunohistochemistry. However, several previous studies have shown that mutations of the p53 tumor suppressor gene are either significantly less frequent than in other tumors [24,25] or are totally absent in RCC [23]. Therefore, alternative pathways may have caused p53 stabilization in RCC.…”

Smoking negatively impacts renal cell carcinoma overall and cancer‐specific survival

“…Moreover, previous reports indicated that p53 expression is detectable by IHC in 20% to 50% of renal tumors,11‐13, 15 and the amount of p53 expression reportedly is an important prognostic factor in ccRCC 10. However, in some studies, p53 mutation analyses have suggested that the increased p53 expression observed in RCC can occur independent of p53 mutations,10 but this observation was based only on 2 small analyses in which the presence of p53 mutations was correlated with p53 staining in mixed histologic subpopulations 32, 33…”

p53 and MDM2 in renal cell carcinoma

“…For comparison, in other tumors, the reported incidence of p53 mutations typically has been between 60% and 65% for lung and colon cancers; between 40% and 45% for stomach, esophageal, and bladder cancers; between 25% and 30% for breast, liver, and prostate cancers and lymphomas; and between 10% and 15% for leukemias (further information available at: http://www-p53.iarc.fr/ accessed June 15, 2009) 71. One intriguing observation derives from the study by Chemeris and colleagues, who observed that 0 of 29 RCC samples, all positive for p53 by IHC, had a p53 point mutation 50. However, in another study, Zhang and colleagues observed that 44% of tumors with p53 staining (n = 16) had a p53 point mutation 45.…”