title: Correlation of p16 hypermethylation with p16 protein loss in sporadic gastric carcinomas.
abstract: Hypermethylation of p16 has been detected frequently in a variety of cancer cells and is known to repress the level of p16 transcription. In human gastric carcinoma (GC) cells, p16 protein loss has often been detected, but genetic alterations of p16 are infrequent. To investigate the molecular mechanism of p16 gene inactivation in gastric carcinogenesis, we examined the methylation status of p16 in GC using methylation-specific PCR. Thirty-seven of eighty-eight (42%) GC showed p16 hypermethylation. Immunohistochemical analysis of 41 cases of GC showed a complete loss of p16 immunoreactivity in 19 of 22 (86%) methylation-positive cases, but in only 2 of 19 (11%) methylation-negative cases. Of 88 GC, 21 cases were previously identified as having microsatellite instability (MSI). Interestingly, 13 of 21 (62%) MSI-positive tumors and 24 of 67 (36%) MSI-negative tumors had hypermethylation on p16. The relatively high frequency of hypermethylation on p16 and the strong correlation between the immunoreactivity and methylation patterns suggest that methylation is an important mechanism for p16 gene inactivation in GC.
authors.affiliation: Department of Diagnostic Pathology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea. yshim@www.amc.seoul.kr
authors.forename: Y H
authors.initials: YH
authors.lastname: Shim
authors.forename: G H
authors.initials: GH
authors.lastname: Kang
authors.forename: J Y
authors.initials: JY
authors.lastname: Ro
mesh_terms: D001483:Base Sequence; D002899:Chromosomes, Human, Pair 9; D018899:CpG Islands; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D019175:DNA Methylation; D019942:Genes, p16; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16