OVEREXPRESSION OF P53 MESSENGER-RNA IN COLORECTAL-CANCER AND ITS RELATIONSHIP TO P53 GENE MUTATION

We analysed the frequency of p53 mRNA overexpression in a series or 10 9 primary colorectal carcinomas and its association with p53 gene muta tion, which has been correlated with short survival. Sixty-nine of the 109 cases (63%) demonstrated p53 mRNA overexpression, without any cor relation with stage or site of disease. Comparison with p53 gene mutat ion indicated that, besides cases in which p53 gene mutation and p53 m RNA overexpression were either both present (40 cases) or both absent (36 cases), there were also cases in which p53 mRNA was overexpressed in the absence of any mutation (29 cases) and those with a mutant gene in which the mRNA was not overexpressed (four cases). Moreover, the m utant p53 tumours exhibited an increase of p53 mRNA expression, which was significantly higher in tumours expressing the mutated allele alon e than in tumours expressing both wild- and mutated-type alleles. Thes e data (1) show that p53 mRNA overexpression is a frequent event in co lorectal tumours and is not predictive of the status of the gene, i.e. whether or not a mutation is present; (2) provide further evidence th at p53 protein overexpression does not only result from an increase in the half-life of mutated p53 and suggest that inactivation of the p53 function in colorectal cancers involves at least two distinct mechani sms, including p53 overexpression and/or mutation; and (3) suggest tha t p53 mRNA overexpression is an early event, since it is not correlate d with Dukes' stage.