Hyperplastic Polyps and Sessile Serrated Adenomas as a Phenotypic Expression of MYH-Associated Polyposis

被引:139
作者
Boparai, Karam S. [1 ,2 ]
Dekker, Evelien [2 ]
van Eeden, Susanne [1 ]
Polak, Mirjam M. [1 ]
Bartelsman, Joep F. W. M. [2 ]
Mathus-Vliegen, Elisbeth M. H. [2 ]
Keller, Josbert J. [2 ]
van Noesel, Carel J. M. [1 ]
机构
[1] Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol & Hepatol, NL-1105 AZ Amsterdam, Netherlands
关键词
D O I
10.1053/j.gastro.2008.09.020
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: MYH-associated polyposis (MAP) is a disorder caused by a bi-allelic germline MYH mutation, characterized by multiple colorectal. adenomas. These adenomas typically harbor G:C -> T:A transversions in the APC and K-ras genes caused by MYH deficiency. Occasional hyperplastic polyps (HPs) have been described in MAP patients but a causal relationship has never been investigated. We examined the presence of HPs and sessile serrated adenomas (SSAs) in 17 MAP patients and studied the occurrence of G:C -> T:A transversions in the APC and K-ras gene in these polyps. Methods: MAP patients were analyzed for the presence of HPs/SSAs. APC-mutation cluster region and K-ras codon 12 mutation analysis was performed in adenomas (n = 22), HPs (n = 63), and SSAs (n = 10) from these patients and from a control group of sporadic adenomas (n = 17), HPs (n = 24), and SSAs (n = 17). Results: HPs/SSAs were detected in 8 of 17 (47%) MAP patients, of whom 3 (18%) met the criteria for hyperplastic polyposis syndrome. APC mutations were detected only in adenomas and comprised exclusively G:C-T:A transversions. K-ras mutations were detected in 51 of 73 (70%) HPs/SSAs in MAP patients, compared with 7 of 41 (17%) sporadic HPs/SSAs in the control group (P < .0001). In HPs/SSAs, 48 of 51 (94%) K-ras mutations showed G:C-T:A transversions, compared with 2 of 7 (29%) sporadic HPs/SSAs in the control group (P < .0001). Conclusions: HPs and SSAs are a common finding in MAP patients. The detection of almost exclusively G:C -> T:A transversions in the K-ras gene of HPs/SSAs strongly suggests that these polyps are related causally to MTH deficiency. This implies that distinct pathways, that is, APC-gene related in adenomas and nonrelated in HPS/SSAs, appear to be operational in MAP.
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页码:2014 / 2018
页数:5
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