LOW-FREQUENCY OF P53 GENE MUTATION AND PROTEIN EXPRESSION IN MUCINOUSCOLORECTAL CARCINOMAS

Immunohistochemical data indicate that the frequency of p53 protein ov erexpression is consistently lower in the mucinous than in the non-muc inous carcinomas of the breast, ovary, pancreas and colon. This peculi ar immunohistochemical behavior of the mucinous phenotype could be due to the effect of large amounts of mucus on the staining or to an actu al mutation frequency difference between mucinous and non-mucinous car cinomas. This question was investigated on a group of mucinous colorec tal carcinomas. DNA was extracted from paraffin sections of 16 human m ucinous colorectal carcinomas and the mutation frequency was determine d by sequencing of p53 exons amplified in PCR. The expression of p53 p rotein was determined with the avidin-biotin complex-peroxidase staini ng procedure and CM-I antiserum. Twenty-five percent of the tumors exh ibited p53 protein overexpression and in 31% a mutation was detected. Concordance between the two techniques was found in 69% of tumors. Ove rexpression without mutation was observed in 12% and mutation without overexpression in 19%. G:C --> A:T transitions represented the most fr equent lesion (80%), as previously observed in non-mucinous colorectal carcinomas. These data indicate that the mutation pattern in the p53 gene is similar in mucinous and non-mucinous colorectal carcinomas. Th e low frequency of p53 overexpression in the mucinous phenotype is not due to a mucus effect on the staining but is related to the low mutat ion frequency of p53 gene. These results lead to the hypothesis that i n contrast to the non-mucinous tumors the development of the majority of colonic carcinomas with the mucinous phenotype may be independent f rom p53 mutations.