A DETAILED ANALYSIS OF THE ROLE OF K-RAS GENE MUTATION IN THE PROGRESSION OF COLORECTAL ADENOMA

To elucidate the role of ras gene mutations during the early stage of colorectal tumour progression, K-ras gene mutations were analysed in 3 2 benign adenomas and 36 adenomas with focal carcinoma in the colorect um by microscraping of histologically pure regions from tissue section s, polymerase chain reaction-restriction fragment length polymorphism and in part by direct sequencing. Several regions were scraped out and analysed when an adenoma contained areas with different grades of dys plasia. The frequencies of K-ras gene mutation in mild dysplasia, mode rate dysplasia and focal carcinoma were 19% (7/36), 51% (25/49) and 39 % (14/36) respectively. The K-ras gene status was heterogeneous in 4 o f the 11 benign adenomas from which multiple samples were obtained, an d mutations were always found in the regions with more advanced dyspla sia in these adenomas. Thirteen of the 36 adenomas with focal carcinom a showed heterogeneity of mutations between the adenoma region and the focal carcinoma. Seven of which had mutations only in the adenoma reg ion. These findings indicated that the K-ras gene mutations occur duri ng the late stage of adenoma progression and may confer a more advance d morphological phenotype of adenoma, but these mutations are not main ly involved in malignant transformation from adenoma to carcinoma.