Identification of p53 Gene Mutations in Bladder Cancers and Urine Samples

Abstract

Although bladder cancers are very common, little is known about their molecular pathogenesis. In this study, invasive bladder cancers were evaluated for the presence of gene mutations in the p53 suppressor gene. Of 18 tumors evaluated, 11 (61 percent) were found to have genetic alterations of p53. The alterations included ten point mutations resulting in single amino acid substitutions, and one 24-base pair deletion. In all but one case, the mutations were associated with chromosome 17p allelic deletions, leaving the cells with only mutant forms of the p53 gene products. Through the use of the polymerase chain reaction and oligomer-specific hybridization, p53 mutations were identified in 1 to 7 percent of the cells within the urine sediment of each of three patients tested. The p53 mutations are the first genetic alterations demonstrated to occur in a high proportion of primary invasive bladder cancers. Detection of such mutations ex vivo has clinical implications for monitoring individuals whose tumor cells are shed extracorporeally.

p53 immunodetection of liquid-based processed urinary samples helps to identify bladder tumours with a higher risk of progression

“…The first studies of p53 alterations in the urine used a cloning approach followed by sequencing to confirm the presence of mutations (Sidransky et al, 1991). Thereafter, several reports have compared mutations in tissue samples with those found in the urine: p53 gene mutation in the urine has been shown to correlate with tumour recurrence or residual (Sachs et al, 2000).…”

Comparison of the WHO/ISUP Classification and Cytokeratin 20 Expression in Predicting the Behavior of Low-Grade Papillary Urothelial Tumors

“…The main drawback has been lack of specificity, with expression of Lewis X antigen frequently observed in reactive urothelium (15). Detection of p53 mutations, which are frequently manifest as increased intracytoplasmic protein detected by immunohistochemistry, has similarly been suggested as a marker of transitional cell neoplasia (16), but use of immunohistochemical detection suffers from both lack of sensitivity and specificity (17). Direct mutation analysis of the p53 gene is too expensive for use as a routine diagnostic test with available technologies.…”

TP53 alterations and patterns of carcinogen exposure in a U.S. population‐based study of bladder cancer

“…2 Interestingly, there is marked urban-rural difference in the incidence rates of bladder cancer, and in the U.S., there is a striking persistence of elevated mortality rates in New England that remains etiologically obscure. 6 The most frequently documented somatic genetic alteration in bladder cancer is in the TP53 gene, with the prevalence of alterations reported varying from 14% 10 to 61% 7 with the populationbased series reporting lower prevalence rates. Most studies of TP53 alteration have been derived from relatively small, hospitalbased series, [8][9][10][11][12] capturing higher stage patients undergoing surgery for their disease.…”