Loss of heterozygosity and microsatellite instability in de novo versus ex-adenoma carcinomas of the colorectum

Small adenocarcinomas of the colorectum showing no evidence of origin from an adenoma have been called de novo carcinomas, a name that implies an orig in via a different molecular genetic mechanism than the usual colorectal ca rcinoma which develops from an adenoma. Using microsatellite analysis, 35 e arly (pT1) de novo and 36 pT1 ex-adenoma carcinomas were compared using 8 m icrosatellite loci at 6 different chromosomal loci (lp, 2p, 8p, 5q, 17p, an d 18q) known or hypothesized to be important for colorectal carcinogenesis. The rate of loss of heterozygosity (LOH) at the 17p locus (near the p53 ge ne) was significantly higher in the de novo than in the ex-adenoma group (7 3 vs. 37%,P = 0.004). The rates of LOH at the other loci (including the APC and DCC genes) and the rate of MSI were not significantly different in the two groups. These results indicate that de novo carcinomas of the colorect um develop via a similar carcinogenetic pathway as conventional ex-adenoma carcinomas; however, their higher rate of LOH at 17p is evidence for a biol ogically more advanced lesion with more frequent p53 mutations, consistent with clinicopathological data indicating that de novo carcinomas are more a ggressive than ex-adenoma carcinomas.