THE SIGNIFICANCE OF P53 GENE MUTATIONS AND EXPRESSIONS IN HUMAN COLORECTAL TUMORS

Using a polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) approach we analyzed 18 human colorectal adenocarcinomas for mutations in exons 5,6,7,8 of p53 gene. At the same time, p53 gene product expression was studied immunohistochemically in these 18 case in frozen sections. The expression of p53 protein was also immunohistochemically studied in formalin-fixed paraffin embeded specimens of 76 colorectal adenocarcinomas and 112 colorectal polyps. Eight out of 18 cases (44%) showed a variant band indicative of a mutation in exons 5-6 of p53 gene 7 out of 8 cases (88%) with p53 gene mutations were positivelystanined for p53. There was no significant correlation between p53. expression and elinicopathological manifestations and prognosis, but the strongest staining was encountered in those cases with well differentiated and early stage adenoearcinomas, while weaker staining was encountered in poorly differentiated and mucoid adenocareinomas, p53 expression was not observed in proliferative polyps and adenomas with low grade dysplasia. The frequency of p53 expression reached 88% (P<0.001) when adenoma showed malignant change, Among three types of adenomas, p53 expression was most frequent in villous type (P<0.05). The frequencies of p53 expression in adenoma, adenoma with malignant change and adenocarcinoma were 4%, 88% and 51% respectively. These indicate that genetic changes of p53 gene play an important role in the transformation from benign adenoma to adenocarcinoma, p53 immunohistochemistry can be used as a surrogate marker for p53 gene mutation for early discovery ofcolorectal adenocarcinomas.