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The serrated pathway to colorectal carcinoma: current concepts and challenges
Author(s) -
Bettington Mark,
Walker Neal,
Clouston Andrew,
Brown Ian,
Leggett Barbara,
Whitehall Vicki
Publication year - 2013
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/his.12055
Subject(s) - kras , microsatellite instability , cancer research , biology , colorectal cancer , dysplasia , phenotype , pathology , carcinoma , mutation , cancer , medicine , genetics , gene , microsatellite , allele
Approximately 30% of colorectal carcinomas develop via a serrated neoplasia pathway, named for the pattern of crypts in the precursor polyps. Molecular abnormalities consistently involve methylation of C p G islands [ C p G island methylator phenotype ( CIMP )] of low degree ( CIMP ‐ L ) or high degree ( CIMP ‐ H ), and activating mutations of the mitogen‐activated protein kinase pathway components BRAF or KRAS . Microsatellite instability ( MSI ) of a high level ( MSI ‐ H ) is often present, allowing for a molecular classification of serrated pathway carcinoma as: (i) BRAF mutant/ CIMP ‐ H with either a) MSI ‐ H or b) microsatellite stable ( MSS ); and (ii) KRAS mutant/ CIMP ‐ L / MSS . Precursor polyps include sessile serrated adenoma ( SSA ), characterized by proximal location, crypt architectural disturbance, and BRAF mutation. Microvesicular hyperplasic polyp ( MVHP ) probably precedes the development of SSA , and borderline lesions between MVHP and SSA occur. Cytological dysplasia in SSA portends advanced genetic abnormality and a high risk of progression to carcinoma. The traditional serrated adenoma has a predilection for the left colon, tubulovillous architecture, eosinophilic cytoplasm, and frequent KRAS mutation. Serrated morphology carcinoma is a new W orld H ealth O rganization subtype with well‐differentiated, mucinous or trabecular patterns. It has frequent KRAS or BRAF mutations and a poor prognosis. This review provides an insight into the histology and molecular mechanisms driving these serrated pathway lesions.