title: Correlation of laterally spreading type and JC virus with methylator phenotype status in colorectal adenoma.
abstract: Accurate frequencies of CpG island methylator phenotype (CIMP) have not been determined for laterally spreading tumors (LSTs) and other flat-type colorectal adenomas, and the role of JC virus T-antigen (T-Ag) in these tumors is unclear. We used MethyLight assay to analyze the relationship between CIMP status and clinicopathologic characteristics in tissue from 72 LST of granular-type (LST-G), 35 LST of nongranular-type (LST-NG), 54 protruded-type adenomas, and 89 colorectal cancers. We also investigated the relationship between CIMP status and T-Ag by immunohistochemistry. With the use of 5 markers for CIMP status, tumors were classified as CIMP-high (> or = 4/5 methylated promoters), CIMP-low (1/5 to 3/5 methylated promoters), or CIMP-0 (no methylated promoters). The proportion classified as CIMP-0 status was 5.6% for protruded-type adenoma, 17.1% for LST-NG, and 29.2% for LST-G (LST-G versus protruded-type adenoma, P = .001). CIMP-low status was established for 62.5% of LST-G, 74.3% of LST-NG, and 81.5% of protruded-type adenomas. CIMP-high status was established for 8.3% of LST-G, 8.6% of LST-NG, and 12.9% of protruded-type adenomas. The proportions of CIMP-low and CIMP-high status were not significantly different between the 3 groups. Multiple logistic analysis showed that LST-G appearance was the only significant factor for identifying CIMP-0 status. BRAF mutation was the only significant factor for identifying CIMP-high status. T-Ag expression increased with CIMP status and was not associated with macroscopic appearance. In conclusion, among colorectal adenomas, CIMP-high status was determined by BRAF mutation and not by macroscopic type, unlike CIMP-0. JC virus T-Ag may be important in determining methylator phenotype.
authors.affiliation: First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan. nosho@sapmed.ac.jp
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Nosho
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Taiga
authors.initials: T
authors.lastname: Takahashi
authors.forename: Masashi
authors.initials: M
authors.lastname: Mikami
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hizaki
authors.forename: Tadateru
authors.initials: T
authors.lastname: Maehata
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamaoka
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Adachi
authors.forename: Fumio
authors.initials: F
authors.lastname: Itoh
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Imai
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Shinomura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000236:Adenoma / Q000235:genetics* / Q000473:pathology*; D000368:Aged; D000957:Antigens, Viral, Tumor / Q000235:genetics*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D018899:CpG Islands / Q000502:physiology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007577:JC Virus / Q000276:immunology*; D008297:Male; D008745:Methylation; D008875:Middle Aged; D015999:Multivariate Analysis; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018168:Receptors, Retinoic Acid / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000957:Antigens, Viral, Tumor; D051792:Basic Helix-Loop-Helix Proteins; D020747:Calcium Channels, T-Type; D019941:Cyclin-Dependent Kinase Inhibitor p16; D000070957:MutL Protein Homolog 1; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018168:Receptors, Retinoic Acid; D018631:ras Proteins; C121855:CACNA1G protein, human; C117307:KRAS protein, human; C501486:MLH1 protein, human; C105389:NEUROG1 protein, human; C082927:retinoic acid binding protein I, cellular; C482119:BRAF protein, human