Abstract
Aims. To compare methylation profiles, protein expression, and microsatellite instability (MSI) of sporadic, HNPCC, and familial hyperplastic polyps (HPs). Methods. Methylation-specific PCR (MSP) and pyrosequencing assessed p16, MGMT, hMLH-1, MINT 1, and MINT 31 methylation. IHC (Immunohistochemistry) assessed Ki67, CK20, hMLH-1, hMSH-2, and hMSH-6 protein expression. MSI analysis was performed on those polyps with adequate DNA remaining. Results. 124 HPs were identified 78 sporadic, 21 HNPCC, 25 familial, and the HNPCC group demonstrated no significant differences in overall methylation (P = .186 Chi2). The familial group demonstrated significantly less over all methylation levels (P = .004 Chi2). Conclusions. HPs that occur in HNPCC have no more worrying features at a molecular level than those patients with HPs in a sporadic setting.
Highlights
For many years hyperplastic polyps (HPs) have been considered innocuous lesions
HPs that occur in HNPCC have no more worrying features at a molecular level than those patients with HPs in a sporadic setting
The adenoma carcinoma sequence was believed to be the mechanism by which most or all colorectal cancer (CRC) occurred; this sequence described a series of mutations in genes resulting in an increasingly dysplastic adenoma progressing to CRC over time
Summary
Recent pathological and molecular observations have challenged this and given rise to the serrated adenoma carcinoma sequence. The reported accumulation of genetic changes described in the adenoma-carcinoma sequence [1] does not wholly account for neoplastic transformation within the colon [2,3,4]. Mutation of the mismatch repair genes (most commonly MLH-1 and MSH-2) leading to MSI (microsatellite instability) in CRC is an alternative mechanism underlying tumour formation in patients with HNPCC [5]. It is known that up to 15% of sporadic CRC have MSI; not as a consequence of mutation in the mismatch repair genes but through a process of epigenetic changes to MLH-1 [6]
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