Combined p53/Bax mutation results in extremely poor prognosis in gastric carcinoma with low microsatellite instability

Item Type:	Article
Title:	Combined p53/Bax mutation results in extremely poor prognosis in gastric carcinoma with low microsatellite instability
Creators Name:	Mrozek, A. and Petrowsky, H. and Sturm, I. and Kraus, J. and Hermann, S. and Hauptmann, S. and Lorenz, M. and Doerken, B. and Daniel, P.T.
Abstract:	Gastric cancer is highly refractory to DNA-damaging therapies. We therefore studied both gene mutation and protein expression of p53 and Bax in a cohort of 116 patients with gastric cancer who underwent R0-resection with a curative intent. Bax mutation was independent from severe microsatellite instability (MSI), that is, global mismatch repair deficiency as determined by analysis of BAT-25/BAT-26 microsatellite markers. Thus, Bax-frameshift mutation is a feature of tumors with low MSI. In contrast and as expected, no p53 mutations were observed in the microsatellite instable tumors. p53 Mutation or p53 overexpression did not have an impact on disease prognosis. p53-Inactivation was, however, associated with an extremely poor prognosis in the subgroup of patients with Bax-mutated tumors. Thus, we show for the first time that the combined mutation of p53 and Bax, two key regulators of the mitochondrial apoptosis pathway, results in an extremely aggressive tumor biology and poor clinical prognosis.
Keywords:	Bax, p53, Mutation, Gastric carcinoma, DNA mismatch repair (MMR) deficiency, Microsatellite instability (MSI), Prognosis
Source:	Cell Death and Differentiation
ISSN:	1350-9047
Publisher:	Nature Publishing Group
Volume:	10
Number:	4
Page Range:	461-467
Date:	1 April 2003
Official Publication:	https://doi.org/10.1038/sj.cdd.4401193
PubMed:	View item in PubMed

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