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Microsatellite instability in esophageal squamous cell carcinoma is not associated with hMLH1 promoter hypermethylation
Author(s) -
Hayashi Masahiro,
Tamura Gen,
Jin Zhe,
Kato Izumi,
Sato Makoto,
Shibuya Yoichiro,
Yang Suran,
Motoyama Teiichi
Publication year - 2003
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1046/j.1440-1827.2003.01478.x
Subject(s) - microsatellite instability , loss of heterozygosity , dna methylation , immunohistochemistry , dna mismatch repair , biology , methylation , cancer research , tumor suppressor gene , microsatellite , microbiology and biotechnology , polymerase chain reaction , dna repair , pathology , gene , carcinogenesis , gene expression , medicine , genetics , allele , immunology
To test whether a subset of esophageal squamous cell carcinomas (SCC) develop through a deficiency in DNA mismatch repair, we examined microsatellite instability (MSI) using 11 microsatellite markers including BAT‐26 , hMLH1 protein expression by immunohistochemistry, and methylation status of the hMLH1 promoter by methylation‐specific polymerase chain reaction (MSP). p53 mutations were also investigated. Microsatellite instability at one or more loci was observed in 40% (12/30) of esophageal SCC tumor samples, although only one of these tumors was categorized as high‐frequency MSI (MSI‐H) and none showed BAT‐26 instability. While immunohistochemistry revealed decreased hMLH1 protein expression in 27% (8/30) of the tumors, hMLH1 promoter hypermethylation was not observed. Absence of hMLH1 protein expression was relatively common in well‐differentiated (keratinizing‐type) esophageal SCC, but was not associated with hMLH1 promoter hypermethylation. p53 mutation was detected in 37% (11/30) and loss of heterozygosity (LOH) in 90% (27/30) of esophageal SCC samples. Our results suggested that most esophageal SCC develop through defects in tumor suppressor genes (i.e. the suppressor pathway), and that MSI in esophageal SCC probably represent random replication errors rather than being associated with DNA mismatch repair deficiency.