p53 mutation, but not p53 overexpression, correlates with survival in head and neck squamous cell carcinoma

Abstract

Summary Survival in squamous cell carcinoma of the head and neck (HNSCC) was compared with overexpression and mutation of the p53 gene. Archival tissue from 77 tumours was analysed for protein expression using immunohistochemistry (IHC) with the monoclonal antibody Do-7, and for the presence of mutation in exons 5-8 using single-stranded conformation polymorphism (SSCP), followed (4/19) or low protein expression (4/33). Fifty-eight patients were eligible for survival analysis. There was a strong correlation between p53 mutation and cause-specific survival; median survival among mutated cases was 12.5 months compared with >160 months among non-mutated patients (P < 0.005). There was no correlation between p53 overexpression and survival. The results suggest that p53 mutation status is an important prognostic factor in HNSCC, and that IHC analysis of protein overexpression is an inadequate measure of gene mutation in these tumours.

Prognostic value of p53 mutations, bax, and spontaneous apoptosis in maxillary sinus squamous cell carcinoma

“…53 Therefore, mutational analysis of p53 by direct sequencing is more likely to be accurate and reliable than immunohistologic methods. 20,48,54 However, the analysis is problematic in that normal cells without mutations may present around tumor cells with p53 mutation in the samples, resulting in a lower detection of mutation genes. The laser capture microdissection system employed in the current study could solve the problem.…”

“…In advanced laryngeal carcinoma, Bradford et al 58 reported that p53 mutation is associated with a poor prognosis. In head and neck SCC besides maxillary sinus SCC, Mineta et al 20 showed p53 mutation to be an independent risk factor for disease specific death. In the current study, the univariate analysis and the KaplanMeier method showed that p53 mutation was closely associated with poor disease-free survival in maxillary sinus SCC.…”

“…Some studies showed no correlation, 19,26 -28 whereas others showed a significant correlation between p53 expression and prognosis. 21,29,30 Conversely, a majority of studies showed an association of p53 mutation with poor prognosis, 20,31 but some studies showed that there is no association between p53 mutation and prognosis. 19 Overexpression of bcl-x has been reported to protect tumor cells from apoptosis, 32 whereas increased bax expression promotes apoptosis induced by cytotoxic drugs and radiation.…”

Combined expression of p53, cyclin D1 and epidermal growth factor receptor improves estimation of prognosis in curatively resected oral cancer

“…Our data, however, confirmed the results of previous studies that failed to establish an association of p53 expression with survival in head and neck cancers. 31,32 The absence of an impact of p53 expression on tumor progression might possibly be explained by recent studies that report the predictive value of p53 mutation 33 and mutation within DNA-binding surface region of p53 34 for shortened survival rather than p53 protein expression in head and neck cancers. More comprehensive studies combined with mutational analysis are required for determining the outcomes of cancer patients using immunohistochemistry.…”

Molecular markers in clinical radiation oncology

“…Tumor cells with mutations in the P53 gene generally result in accumulation and overexpression of the P53 protein (Iggo et al, 1990;Lane, 1992;Wilson et al, 1995;Koch et al, 1996;Silvestrini, 1996;Dumaz et al, 1997;Mineta et al, 1998;Gallo et al, 1999;Saunders et al, 1999;Taylor et al, 1999;Obata et al, 2000;Agarwal et al, 2001). However, there is often discordance between the mutation status of the P53 gene and the evaluation of the protein levels (i.e., expression of the protein does not always correlate with underlying mutations, and underlying P53 mutations may not always result in overexpression of the protein).…”