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|Title:||Microsatellite instability and MLH1 hypermethylation - Incidence and significance in colorectal polyps in young patients|
|Authors:||Koh, D.C. |
|Citation:||Koh, D.C., Luchtefeld, M.A., Kim, D.G., Attal, H., Monroe, T., Ingersoll, K. (2007-07). Microsatellite instability and MLH1 hypermethylation - Incidence and significance in colorectal polyps in young patients. Colorectal Disease 9 (6) : 521-526. ScholarBank@NUS Repository. https://doi.org/10.1111/j.1463-1318.2007.01175.x|
|Abstract:||Objective: Microsatellite instability (MSI) is observed in most hereditary nonpolyposis colorectal cancer-related colorectal cancers (CRC). The original Bethesda criteria recommends MSI testing in patients ≤40 years diagnosed with adenomas. We aimed to determine the incidence of MSI and the presence of hypermethylation of the promoter site of the MLH1 gene in these polyps. Method: Patients aged ≤40 years diagnosed with colonic polyps removed endoscopically from 1998 to 2003 were identified and their charts reviewed. DNA extractions were performed and tested for MSI at the Bethesda Consensus recommended loci. Samples were characterized by immunohistochemical staining of the four mismatch repair (MMR) proteins. MLH1 hypermethylation was assessed using a real-time methylation-specific polymerase chain reaction (PCR). The appropriate statistical analyses were applied. Results: 23 patients with 38 polyps were analysed. Eight patients had a positive family history colorectal polyp, 11 a family history of CRC. No significant correlation between a family history of colorectal polyps or cancer and polyp location was found. About 53% of the polyps were tubulo-adenomas and 27% tubulovillous adenomas. Immunohistochemistry (IHC) staining revealed appropriate expression of the MMR proteins in all samples. None of the polyps exhibited MSI. MLH1 'A' hypermethylation was present in 16% of the polyps. No hypermethylation was observed at region 'C'. A positive family history of colorectal polyps and cancer were associated with a higher incidence of MLH1 'A' hypermethylation. There was no determinable correlation between the clinico-pathological features of the polyp with MLH1 hypermethylation. Conclusion: MLH1 HM was found in approximately 16% of polyps found in young patients and represents one of the epigenetic changes that may result in the subsequent progression to carcinoma along an accelerated sequence. The yield of MSI testing in these patients is low and is not recommended. © 2007 The Association of Coloproctology of Great Britain and Ireland.|
|Source Title:||Colorectal Disease|
|Appears in Collections:||Staff Publications|
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