Correlation of laterally spreading type and JC virus with methylator phenotype status in colorectal adenoma.
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.
Nosho
Katsuhiko
K
First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan. nosho@sapmed.ac.jp
Yamamoto
Hiroyuki
H
Takahashi
Taiga
T
Mikami
Masashi
M
Hizaki
Keiichi
K
Maehata
Tadateru
T
Taniguchi
Hiroaki
H
Yamaoka
Satoshi
S
Adachi
Yasushi
Y
Itoh
Fumio
F
Imai
Kohzoh
K
Shinomura
Yasuhisa
Y
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
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