BACKGROUND/AIMS: Mutations in p53, a tumor suppressor gene located on chromosome 17p, are the most frequent genetic alterations found in human cancers. Increased intracellular concentration of p53, which is frequently but not systematically related to p53 mutation, has been proposed to be associated with poor prognosis in some tumor types. In colorectal cancer, this significance is still a matter of debate. To directly investigate the relationship between prognosis and p53 mutation, this study screened a series of 85 colorectal carcinomas for mutations in exons 5-8 of this gene. METHODS: Polymerase chain reaction-amplified products from tumor DNA were analyzed by denaturing gradient gel electrophoresis and direct DNA sequencing. RESULTS: Forty-four tumors were found to be mutated (52%). A strong correlation between the presence of a mutation and short survival was observed (P = 0.003). When tumors were classified according to their histological stage, a multivariate Cox model analysis showed that p53 mutation, rather than 17p allelic loss (previously proposed to convey prognostic information), was retained as the only independent prognostic factor (relative risk, 2.25; 95% confidence interval, 1.06-4.80; P < 0.029). CONCLUSIONS: Combined with staging, direct monitoring of p53 mutation improves prognostic accuracy for colorectal cancer.
BACKGROUND/AIMS: Mutations in p53, a tumor suppressor gene located on chromosome 17p, are the most frequent genetic alterations found in humancancers. Increased intracellular concentration of p53, which is frequently but not systematically related to p53 mutation, has been proposed to be associated with poor prognosis in some tumor types. In colorectal cancer, this significance is still a matter of debate. To directly investigate the relationship between prognosis and p53 mutation, this study screened a series of 85 colorectal carcinomas for mutations in exons 5-8 of this gene. METHODS: Polymerase chain reaction-amplified products from tumor DNA were analyzed by denaturing gradient gel electrophoresis and direct DNA sequencing. RESULTS: Forty-four tumors were found to be mutated (52%). A strong correlation between the presence of a mutation and short survival was observed (P = 0.003). When tumors were classified according to their histological stage, a multivariate Cox model analysis showed that p53 mutation, rather than 17p allelic loss (previously proposed to convey prognostic information), was retained as the only independent prognostic factor (relative risk, 2.25; 95% confidence interval, 1.06-4.80; P < 0.029). CONCLUSIONS: Combined with staging, direct monitoring of p53 mutation improves prognostic accuracy for colorectal cancer.
Authors: P Hammel; B Boissier; M T Chaumette; P Piedbois; N Rotman; J C Kouyoumdjian; R Lubin; J C Delchier; T Soussi Journal: Gut Date: 1997-03 Impact factor: 23.059
Authors: S Olschwang; R Hamelin; P Laurent-Puig; B Thuille; Y De Rycke; Y J Li; F Muzeau; J Girodet; R J Salmon; G Thomas Journal: Proc Natl Acad Sci U S A Date: 1997-10-28 Impact factor: 11.205
Authors: Y T Chen; M J Henk; K J Carney; W D Wong; D A Rothenberger; T Zheng; M Feygin; R D Madoff Journal: J Gastrointest Surg Date: 1997 May-Jun Impact factor: 3.452
Authors: A Syed Sameer; Shakeel ul Rehman; Arshad A Pandith; Nidda Syeed; Zaffar A Shah; Nissar A Chowdhri; Khursheed A Wani; Mushtaq A Siddiqi Journal: Saudi J Gastroenterol Date: 2009 Oct-Dec Impact factor: 2.485