Molecular changes in the Ki-ras and APC genes in colorectal adenomas and carcinomas arising in the same patient

The purpose of this study was to compare the molecular genetic changes in the Ki-ras and adenomatous polyposis coli (APC) genes between adenomas and carcinomas removed from the same patients. This comparison of benign and malignant tissue would enhance understanding of the progression of molecular changes during the development of colorectal malignancy and similarities between paired lesions could be indicative of a common aetiology. The basic procedures used were DNA extraction from wax blocks of removed tissue, followed by polymerase chain reaction (PCR) and gel electrophoresis for mutations in the Ki-ras gene using single strand conformational polymorphism (SSCP); amplification of a CA repeat marker was used to assess for loss of heterozygosity (LOH) of the APC gene. The main findings in 100 adenoma and carcinoma pairs for the Ki-ras gene were as follows: the frequency of Ki-ras mutation in the adenomas increased with increasing villous component, but did not vary in the paired carcinomas; the frequency of Ki-ras mutation in villous adenomas was greater than in carcinomas; and when both paired lesions had Ki-ras mutations, only 44% had the identical mutation. For the APC gene, the incidence of LOH in the adenomas did not vary by histological type; the LOH status of the adenoma was associated with that of the paired carcinoma; but when both paired lesions had LOH of the APC gene, only 50% had LOH for the same allele. In conclusion, these data on paired adenomas and carcinomas suggest that a Ki-ras mutation is not a consistent finding between the adenoma and carcinoma from the same bowel. The development of LOH of the APC gene is a slightly more consistent finding between the pair, but is not always allelic-specific.