K-ras mutation and loss of heterozygosity of the adenomatous polyposis coli gene in patients with colorectal adenomas with in situ carcinoma

BACKGROUND. The majority of colorectal carcinomas, if not all, arise from a benign adenoma. The DNA of the carcinomatous cells frequently has mutation s in several genes. However, it is not exactly clear when during the neopla stic process each mutation develops. An adenoma with an area of in situ car cinoma provides an opportunity to evaluate genetic changes within a single neoplasia whose separate areas are comprised of both the benign adenoma as well as the malignant carcinoma. METHODS. Thirty-seven neoplasms with areas of both benign adenoma and in si tu carcinoma were studied. Both portions were evaluated for loss of heteroz ygosity (LOH) of the adenomatous polyposis coli (APC) gene and for mutation s in codons 12/13 of the K-ras oncogene using the polymerase chain reaction technique. RESULTS. Twenty-eight neoplasms showed no LOH in either portion whereas bot h portions of 4 neoplasms revealed a loss of heterozygosity. In three lesio ns the APC gene was normal in the adenomatous portion but LOH was present i n the carcinomatous portion. Two neoplasms were uninformative for LOH of th e APC gene. Thirteen neoplasms showed the wild-type pattern for the K-ras o ncogene whereas 15 contained the identical mutation in both portions. Of th e remaining nine neoplasms, six had a K-ras mutation in the adenomatous por tion only and three had one pattern in the adenomatous portion and a differ ent pattern in the in situ carcinoma portion. CONCLUSIONS. LOH of the APC gene is an early and persistent feature in the evolution of a benign colorectal adenoma into an in situ carcinoma. There i s less consistency regarding K-ras mutations; one in five in situ carcinoma s contains a K-ras mutation different from that observed in the adenomatous portion. Cancer 1999;86:31-6. (C) 1999 American Cancer Society.