Premium
Colorectal serrated adenocarcinoma
Author(s) -
Mäkinen M J
Publication year - 2007
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2006.02548.x
Subject(s) - microsatellite instability , hyperplastic polyp , adenocarcinoma , colorectal cancer , dna methylation , cancer research , cancer , methylation , biology , mlh1 , adenoma , cpg site , pathology , medicine , dna mismatch repair , gene , genetics , gene expression , colonoscopy , microsatellite , allele
Colorectal cancer (CRC) ranks among the three most common cancers in terms of both cancer incidence and cancer‐related deaths in most Western countries. Serrated adenocarcinoma is a recently described, distinct variant of CRC, accounting for about 7.5% of all CRCs and up to 17.5% of most proximal CRCs. It has been postulated that about 10–15% of sporadic CRCs would have their origin in serrated polyps that harbour a significant malignant potential. These lesions include hyperplastic‐type aberrant crypt foci, hyperplastic polyps, sessile serrated adenomas, admixed polyps and serrated adenomas, and constitute the so‐called ‘serrated pathway’, which is distinct from both the conventional adenoma–carcinoma pathway and the mutator pathway of hereditary non‐polyposis CRC and is characterized by early involvement of oncogenic BRAF mutations, excess CpG island methylation (CIM) and subsequent low‐ or high‐level DNA microsatellite instability (MSI). Methylation of hMLH1 is likely to explain the increased frequency of high‐level MSI (16%) and methylation of MGMT is postulated to explain the low‐level MSI (29%) in serrated adenocarcinomas. Reproducible histopathological criteria for serrated adenocarcinoma have recently been established and they have been qualified by DNA expression analysis for 7928 genes, showing clustering of serrated adenocarcinomas into a molecular entity apart from conventional adenocarcinoma, and representing with distinct down‐regulation of EPHB2 , PTCH and up‐regulation of HIF1α .