Accumulation of Nuclear p53 and Tumor Progression in Bladder Cancer

Abstract

In patients with transitional-cell carcinoma confined to the bladder, an accumulation of p53 in the tumor-cell nuclei detected by immunohistochemical methods predicts a significantly increased risk of recurrence and death, independently of tumor grade, stage, and lymph-node status. Patients with transitional-cell carcinoma confirmed to the bladder that demonstrates nuclear p53 reactivity should be considered for protocols of adjuvant treatment.

Multivariate analysis of survival, recurrence, progression and development of mestastasis in T1 and T2a transitional cell bladder carcinoma

“…In our study, the grade does not appear as an independent prognosis variable. In this aspect, our results are consistent with those included in other multivariate studies, in terms of survival, 6,12,19,21 recurrence, 8,11,[15][16][17][18][19]25 and progression. [21][22][23]25 Our study shows that there are several significant variables in the prognosis of bladder TCC at T1 and T2a classifications.…”

“…Esrig et al 19 and Tsuji et al 20 point to a significant link between the expression of p53 and survival, although the latter study included only a univariate analysis. However, in the studies by Jahnson et al 6 and Liukkonen et al 21 the expression of p53 does not appear as an independent variable of survival.…”

Gene therapy for bladder cancer using E1B-55 kD-deleted adenovirus in combination with adenoviral vector encoding plasminogen kringles 1–5

“…The generally poor prognosis of advanced bladder cancer indicates the need for new therapeutic modalities. Mutations in the p53 gene are the most common genetic defect in human bladder cancer, which occur in approximately 50% of bladder cancer and are associated with highstage, high-grade TCC (Sidransky et al, 1991;Esrig et al, 1994). In accordance with the important role of p53 in bladder carcinogenesis, loss of heterozygosity of 17p, where p53 gene is located, is detected in more than 60% of patients with poorly differentiated tumours (Olumi et al, 1990).…”

Applications of Molecular Diagnostics: Solid Tumor Genetics Can Determine Clinical Treatment Protocols

“…Patients with superficial bladder cancer harboring mutations of the TP53 gene and altered patterns of p53 expression have a more aggressive clinical course (11)(12)(13)(14). Several studies reported that detection of altered p53 expression was associated with disease progression and death due to bladder cancer (12,15). Moreover, these aberrations were found to be independent predictors of recurrence and survival in several of the referred studies.…”

“…Because selection criteria to determine treatment for a particular tumor in a particular patient are incompletely defined, new biologic determinants are needed for proper selection and monitoring of therapy. It has been reported that mutations and altered patterns of p53 expression, or genes involved in the p53 pathways, occur in an important percentage of patients with advanced bladder cancer, ranging from 40 to 70% of these cases (14,15,17,18). Moreover, it has been reported that such alterations may represent a major cause of treat-ment failure and subsequent death (17,18).…”