Changes in known genes do not account for the growth of the majority of SAs. Some SAs may harbour changes in the CRAC1 gene. K-ras mutations may however be less common in SAs than in classical adenomas. SAs rarely show MSI or any evidence of chromosomal-scale genetic instability. In common with classical adenomas, some SAs develop along pathways involving changes in APC/β-catenin. Comparative genomic hybridisation detected no gains or deletions of chromosomal material.Ĭonclusions: The serrated pathway of colorectal tumorigenesis appears to be heterogeneous. Aberrant E-cadherin expression was found in seven polyps. Loss of MGMT expression occurred in 18% of polyps and showed a borderline association with K-ras mutations. K-ras mutations and p53 mutations/overexpression were found in 15% and 8% of SAs, respectively. Wnt pathway abnormalities ( APC mutation/LOH, β-catenin mutation/nuclear expression) occurred in 11 SAs, including 6/31 (19%) non-FAP tumours. Results: MSI was rare (<5% cases) and there was no loss of expression of mismatch repair proteins. Comparative genomic hybridisation was performed on several polyps. Expression patterns of β-catenin, p53, MLH1, MSH2, E-cadherin, and O 6-methylguanine DNA methyltransferase (MGMT) were assessed by immunohistochemistry. We screened these polyps for selected molecular changes, including loss of heterozygosity (LOH) close to APC (5q21) and CRAC1 (15q13-q22), MSI, and mutations of K-ras, APC, p53, and β-catenin. Materials and methods: We analysed 39 SAs from 27 patients, including eight SAs from patients with familial adenomatous polyposis (FAP). Molecular studies comparing SAs and classical adenomas suggest that each may be a distinct entity in particular, it has been proposed that microsatellite instability (MSI) distinguishes SAs from classical adenomas and that SAs and the colorectal cancers arising from them develop along a pathway driven by low level microsatellite instability (MSI-L).Īims: To define the molecular characteristics of SAs of the colorectum. Background: Serrated adenomas (SAs) of the colorectum combine architectural features of hyperplastic polyps and cytological features of classical adenomas.
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