Genetic and Immunophenotype Analyses of TP53 in Bladder Cancer

Abstract

Altered p53 status is a frequent event in bladder cancer and reported to have prognostic significance. We studied the TP53 gene and its product in 76 patients affected with urinary bladder carcinomas by immunohistochemistry (mAb DO-7), polymerase chain reaction single-strand conformational polymorphism (exons 4-8) followed by direct sequencing of shifted bands, and loss of heterozygosity in 17p (p53CA). H-RAS mutations were also studied. The receiver operating characteristic curve and the logistic-regression analysis were used to evaluate the validity of immunohistochemistry in predicting TP53 mutations. A p53-positive nuclear phenotype was defined by a cutoff of 20% tumor cells being immunoreactive and was found in 23 cases, while TP53 mutations were detected in 22 cases, four of them with a negative p53 phenotype. TP53 deletions were identified in 23 cases. No H-RAS gene mutations were observed. There was a significant association between phenotype and genotype results. Moreover, a significant association was observed between p53 status and tumor stage and grade, being alterations more common in high-stage and high-grade tumors (both chi2 test; P < .01). Deletion of 17p significantly correlated with tumor stage (P < .01) and grade (P = .01), allelic losses being more common in advanced disease. Data from these studies suggest that genetic assays are necessary for the optimal determination of TP53 alterations, mainly in tumors with a p53 negative phenotype, and especially in early stage tumors for which p53 status may assist in determining its progression to invasive disease. Since p53 alterations are significantly associated to clinicopathological features of poor prognosis, the inclusion of both p53 phenotype and TP53 mutation status into a predictive panel of tumor markers for bladder cancer is recommended.

Identification of key pathways and genes influencing prognosis in bladder urothelial carcinoma

“…Our results are consistent with three earlier studies that elicited the predictive value of cell cycle regulatory protein expression in the prognosis and progression of BUC 25–27. Alterations of TP53 are predictive for BUC recurrence and are markedly associated with an unfavorable prognosis after radical cystectomy 28,29. GO enrichment analysis for biological processes demonstrated that BUC tumors were associated with mitotic recombination, sister chromatid segregation, and mitotic sister chromatid segregation, all of which are related to cell cycle regulation 30–32.…”

Effects of P-MAPA Immunomodulator on Toll-Like Receptors and p53: Potential Therapeutic Strategies for Infectious Diseases and Cancer

“…The p53 gene and protein expression levels both play a critical role in the regulation of the normal cell cycle, cell cycle arrest, and apoptotic response [77-79]. Alterations in the p53 protein, leading to a loss of its tumor suppressor function, have been reported previously by some authors [79,80].…”

Meta-Analysis of Studies Analyzing the Role of Human Papillomavirus in the Development of Bladder Carcinoma

“…The majority of patients tend to relapse, but a group of patients progress toward muscle-invasive disease [2]. To date, the mechanisms associated with the initiation and progression of these tumors, along with possible risk factors, are not well known [3]. …”