Detection of c-ras gene mutation and expression of p21 protein in dysplasias and carcinomas complicating ulcerative...

Point mutations of c-ras genes and the expression of p21 protein were analyzed in 13 patients with colorectal carcinoma complicating ulcerative colitis; in 12 of the 13, there were dysplastic lesions close to the carcinomas. Point mutations of c-ras genes were studied by polymerase chain reaction and dot blot hybridization with 32p-labeled oligonucleotide probes. Findings indicated mutations of c-Ki-ras at condons 12, 13, and 61 and c-Ha-ras and c-N-ras at condons 12 and 61. The expression of p21 protein was analyzed by immunohistochemical staining using a monoclonal antibody. Only 1 of the 13 patients with carcinoma showed a point mutation, this being from G to A transition at the second position of codon 12 of c-Ki-ras. No point mutations of c-Ki-ras, c-Ha-ras, or c-N-ras were found in other carcinomatous lesions and dysplasias. In the dysplastic or carcinomatous lesions of 11 patients, the increased expression of p21 protein was observed. These results suggest that point mutations of c-ras genes are rare in dysplasias and carcinomas complicating ulcerative colitis and that the increased expression of p21 protein is not always correlated with point mutations of c-ras genes.