The serrated neoplasia pathway of colorectal tumors: Identification of MUC5AC hypomethylation as an early marker of polyps with malignant potential.

The serrated neoplasia pathway accounts for 20-30% of colorectal cancers (CRC), which are characterized by extensive methylation (CpG island methylation phenotype, CIMP), frequent BRAF mutation and high microsatellite instability (MSI). We recently identified MUC5AC mucin gene hypomethylation as a specific marker of MSI CRC. The early identification of preneoplastic lesions among serrated polyps is currently challenging. Here, we performed a detailed pathological and molecular analysis of a large series of colorectal serrated polyps and evaluated the usefulness of mucin genes MUC2 and MUC5AC to differentiate serrated polyps and to identify lesions with malignant potential. A series of 330 colorectal polyps including 218 serrated polyps [42 goblet cell-rich hyperplastic polyps (GCHP), 68 microvesicular hyperplastic polyps (MVHP), 100 sessile serrated adenoma (SSA) and eight traditional serrated adenoma (TSA)] and 112 conventional adenomas was analyzed for BRAF/KRAS mutations, MSI, CIMP, MLH1 and MGMT methylation, and MUC2 and MUC5AC expression and methylation. We show that MUC5AC hypomethylation is an early event in the serrated neoplasia pathway, and specifically detects MVHP and SSA, arguing for a filiation between MVHP, SSA and CIMP-H/MSI CRC, whereas GCHP and TSA arise from a distinct pathway. Moreover, MUC5AC hypomethylation specifically identified serrated lesions with BRAF mutation, CIMP-H or MSI, suggesting that it may be useful to identify serrated neoplasia pathway-related precursor lesions. Our data suggest that MVHP should be recognized among HP and require particular attention.

Renaud F ，Mariette C ，Vincent A ，Wacrenier A ，Maunoury V ，Leclerc J ，Coppin L ，Crépin M ，Van Seuningen I ，Leteurtre E ，Buisine MP ... -  《-》

Comparison of microsatellite instability, CpG island methylation phenotype, BRAF and KRAS status in serrated polyps and traditional adenomas indicates separate pathways to distinct colorectal carcinoma end points.

O'Brien MJ ，Yang S ，Mack C ，Xu H ，Huang CS ，Mulcahy E ，Amorosino M ，Farraye FA ... -  《AMERICAN JOURNAL OF SURGICAL PATHOLOGY》

Molecular features of colorectal hyperplastic polyps and sessile serrated adenoma/polyps from Korea.

Kim KM ，Lee EJ ，Ha S ，Kang SY ，Jang KT ，Park CK ，Kim JY ，Kim YH ，Chang DK ，Odze RD ... -  《-》

BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum.

Kambara T ，Simms LA ，Whitehall VL ，Spring KJ ，Wynter CV ，Walsh MD ，Barker MA ，Arnold S ，McGivern A ，Matsubara N ，Tanaka N ，Higuchi T ，Young J ，Jass JR ，Leggett BA ... -  《-》

BRAF and KRAS Mutations in hyperplastic polyps and serrated adenomas of the colorectum: relationship to histology and CpG island methylation status.

Yang S ，Farraye FA ，Mack C ，Posnik O ，O'Brien MJ ... -  《AMERICAN JOURNAL OF SURGICAL PATHOLOGY》