Colorectal serrated adenocarcinoma.
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 HIF1alpha.
Mäkinen
M J
MJ
Department of Pathology, University of Oulu, Oulu, Finland. markus.makinen@oulu.fi
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000236:Adenoma / Q000235:genetics / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics; D003111:Colonic Polyps / Q000235:genetics / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D018899:CpG Islands; D019175:DNA Methylation; D015254:DNA Modification Methylases; D045643:DNA Repair Enzymes; D006801:Humans; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics; D025521:Tumor Suppressor Proteins
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D025803:Tumor Suppressor Protein p14ARF; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000070957:MutL Protein Homolog 1; D045643:DNA Repair Enzymes