6th ESACP Congress, Heidelberg, April 7-11, 1999

A071
LOSS OF 17P AND GAIN OF 8Q AND 13Q MARK THE TRANSITION FROM ADENOMA TO CARCINOMA IN COLORECTAL MALIGNANT POLYPS
Hermsen M, Weiss MM, Postma C, Meuwissen SGM, Meijer GA, Giaretti W, Baak JPA

Department of Pathology, Academic Hospital Vrije Universiteit, Amsterdam, Netherlands

Knowledge of genomic changes accompanying progression from colorectal adenoma to carcinoma within individual tumors is limited. The aim of the present study was to compare chromosome aberrations in pre-invasive (adenomatous, A) and invasive (carcinomatous, C) components of malignant polyps. CGH analysis showed a higher degree of randomness of chromosome aberrations in A compared to C. This may be explained by the hypothesis that adenomas consist of multiple genetically different subclones, from one of which carcinoma develops. Indeed we found that C often harboured only partly the same changes as the A; sometimes some extra changes were acquired, and sometimes lost (common changes range 55% - 11%). K-ras mutation analysis of eight pairs showed 6 pairs as wildtype in both components, one pair wildtype in the A and mutated in the C, and one pair mutated in the A and wildtype in the C. In order to eliminate the influence of random genetic changes in the evaluation of chromosomal abnormalities, we focussed at those that frequently occur in carcinomas: gain of 8q, 13q, 20q, and loss of 8p, 17p and 18q. Among these events, loss of 17p was always retained and sometimes acquired in the C (75% in A, 93% in C), and gain of 8q and 13q increased remarkably from A to C (13% to 27%, and 27% to 47%, respectively), suggesting that these alterations are important for the transition from adenoma to carcinoma. The present data do not seem to support a prominent role for K-ras mutation at this stage.