p53, p21 and metallothionein immunoreactivities in patients with malignant pleural mesothelioma: correlations with the epidemiological features and prognosis of mesotheliomas with environmental asbestos exposure

Abstract

The aim of this study is to investigate immunoreactivity for p53, p21 and metallothionein in diffuse malignant pleural mesothelioma (DMPM) and to determine the relationships between the age, sex, asbestos exposure time, survival of DMPM patients with environmental asbestos exposure and immunoreactivity to p53, p21 and metallothionein. Sixty-seven histopathologically-confirmed DMPMs, 38 of whom had environmental and 29 had occupational asbestos exposure, were included. The tumour tissue samples were immunostained with antibodies against p53, p21 and metallothionein. Epidemiological data and the survival times for the DMPM patients with environmental asbestos exposures were obtained from hospital records. Thirty-three per cent of the DMPMs were positive for p53, 35% for p21 and 52% for metallothionein. There was no statistical difference between the histological subtypes of DMPM in terms of immunoreactivity for p53, p21 and metallothionein. For p21 and metallothionein there was a statistically significant difference between the exposure characteristics: patients with environmental asbestos exposure had shown more immunopositivity. There were statistically significant differences between age groups and between asbestos exposure times for metallothionein, and between asbestos exposure times and p21. The patients with positive immunostaining had longer exposure times and were older than those having negative immunostaining. The differences between survival of the patients were not statistically significant in terms of the immunohistochemical results for p53, p21 and metallothionein.

Prognostic significance of cyclooxygenase-2 (COX-2) and expression of cell cycle inhibitors p21 and p27 in human pleural malignant mesothelioma

“…17 18 However, p21 and p27 have also been shown to have a significant role in the Cumulative survival progression of human mesothelioma. [20][21][22] Interestingly, while p53 overexpression is a common event in mesothelioma, 24 it is rarely mutated or inactivated. 29 The data presented here showing COX-2 expression as the strongest predictor of a poor outcome not only confirm previous published results but also shed new light on the role of COX-2 in the pathogenesis and progression of mesothelioma.…”

“…18 It has been proposed that COX-2 exerts its influence on mesangial cell proliferation in vitro by a novel mechanism involving the tumour suppressor p53 and the cell cycle inhibitors p21 and p27, 19 and several recent studies have investigated the potential prognostic value of p53, p21 and p27 in malignant mesotheliomas. [20][21][22][23][24] A study was undertaken to analyse the potential prognostic value of the immunohistochemical expression of COX-2 and p27 in 29 malignant mesotheliomas already screened for the expression of p21 and p53 23 24 and for the presence of SV40-like sequences. 25 The correlation with survival of each factor in univariate and multivariate analysis was assessed.…”

Molecular prognostic markers in malignant mesothelioma

“…In a similar manner, the p21 CDK inhibitor has also been found to be differentially expressed in malignant mesothelioma [34,35]. Expression of p21 was initially identified as a protein that was up-regulated by expression of wild type p53 [36].…”

Enhanced Antitumor Therapy by Inhibition of p21waf1 in Human Malignant Mesothelioma

“…In contrast, cancer cells with a defective p21 response undergo cell death that occurs during or after mitosis (8). Previous studies (9) showed that MPM expresses wild-type p21, with a frequency of >35%. In addition, unlike other malignancies, genetic alterations in p53 are rare and gene mutations in the p16…”