Fifty-nine colonic adenomas and 6 hyperplastic colonic polyps were analyzed by single-strand conformation polymorphism analysis for mutations in the adenomatous polyposis coli gene (APC). Frameshifts and premature stop codons in at least one copy of APC were detected in 25 of these adenomas. Five adenomas carried 2 APC mutations. No mutations in APC were found in any of the 6 hyperplastic polyps. The detection of APC mutations increased with size and degree of dysplasia and in rectal as compared to colonic adenomas, although the association was not statistically significant. The frequency of detectable APC mutations was higher in tubulovillous and villous adenomas (10 of 13) than in tubular adenomas (15 of 45) (odds ratio, 6.67; 95% confidence limits, 1.39–41.83; P = 0.005). The significance of the association between the detection of APC mutations and a villous architecture was confirmed in multivariate analysis (relative risk, 6.67; 95% confidence limits, 1.54–28.8; P = 0.005). In conclusion, APC mutation plays a role in adenoma progression; its frequency is significantly higher in lesions with a more villous morphology.

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This work was supported in part by Associazione Italiana per la Ricerca sul Cancro (A. I. R. C.), by Consiglio Nazionale delle Ricerche (C. N. R.) Target Project Applicazioni Cliniche della Ricerca Oncologica contract 93.02279.PF39, by C. N. R. Target Project “Biotechnology and Bioinstrumentation” contract 93.01108PF70, and by C. N. R. Progetto Finalizzato Ingegneria Genetica contract 93.00050.PF99. L. D. B. and V. G. are recipients of A. I. R. C. fellowships. A. B. is a recipient of a “G. Bassani Antivari” (Fondazione Rusconi) fellowship.

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