Clinical value of vesical leukoplakia and evaluation of the neoplastic risk by mutation analyses of the tumor suppressor gene TP53

Abstract

Aim: Leukoplakia has been found to be precancerous in organs covered with squamous epithelium. The present study was conducted to determine whether leukoplakia described in the female bladder is also a premalignant lesion. Methods: Between 1973 and 1996, 77 female patients were diagnosed with vesical leukoplakia by cystoscopy and cytology and were followed-up until 2004 (mean follow-up time: 8.3 years). A survey was conducted to analyze exposure to cocarcinogens. Additionally, DNA was isolated from 36 urine sediments and analyzed for TP53 mutations. The results were compared to the mutation frequency of TP53 in urine sediments from patients diagnosed with transitional cell carcinoma (TCC) of the bladder and healthy controls. Results: The whitish lesion was mostly located at the trigone and varied in size and location during the follow-up years. TP53 mutations were detected in 6 out of 36 urine samples in exons 5, 6 and 7 (mutation frequency: 16.7%). Among control patients with no leukoplakia or TCC of the bladder (n = 70), the spontaneous mutation frequency was similar (14.3%). In contrast, the mutation frequency in patients with TCC of the bladder (n = 148) revealed 39.9% in exons 5, 6, 7 and 8. The present study did not show any statistically significant correlations between chronic inflammations, TP53 mutations, exposure to carcinogens and vesical leukoplakia. Conclusions: Our data suggest that vesical leukoplakia does not necessarily hold neoplastic potential and needs to be clearly distinguished from leukoplakia in other localizations. Therefore, we suggest that a biopsy can be omitted, if follow-up controls by cystoscopy are performed regularly.

Epigenetic markers as promising prognosticators for bladder cancer

“…More sensitive, non-invasive methods are required and many urine-based tumor markers have been developed for use in detecting and monitoring bladder cancers. 19,20,25,[35][36][37][38][39][40][41][42][43][44][45] The Food and Drug Administration (FDA) has already accepted some of these tumor marker tests for use in routine patient care. Initial studies with new markers are usually promising, but subsequent reports often fail to show comparable results.…”

“…Moreover, many researchers found that promoter hypermethylation of CpG islands is associated with development, stage, recurrence, progression, and survival in bladder cancer 10,13,15 . Many urine‐based tumor markers have been developed to provide more sensitive, non‐invasive methods for detecting and monitoring bladder cancers 15–20 . This article focuses on the prognostic relevance of epigenetic markers in bladder cancer (Fig.…”

“…Cytological analysis of voided urine has been the standard non‐invasive method for cancer detection; however, the sensitivity is low, especially for low grade transitional cell carcinomas. More sensitive, non‐invasive methods are required and many urine‐based tumor markers have been developed for use in detecting and monitoring bladder cancers 19,20,25,35–45 . The Food and Drug Administration (FDA) has already accepted some of these tumor marker tests for use in routine patient care.…”

“…10,13,15 Many urine-based tumor markers have been developed to provide more sensitive, non-invasive methods for detecting and monitoring bladder cancers. [15][16][17][18][19][20] This article focuses on the prognostic relevance of epigenetic markers in bladder cancer ( Fig. 1).…”

Toxicological Effects of Tobacco Compounds on the Expression of Genes Involved in Actinic Cheilitis

“…Once mutated TP53 gene undergoes conformational and structural changes that cause a disabling and make it impossible to carry out its function. 41 This deactivation leads to a further stabilization considerably increases the half-life, allowing identification of proteins by immunohistochemistry. Although rare events considered, the presence of mutations "meaningless" or the deletion of both alleles of the gene TP53 prevents its translation due to the production of unstable proteins that interfere directly with its expression and detection.…”