title: Genetic differences stratified by PCR-based microsatellite analysis in gastric intramucosal neoplasia.
abstract: BACKGROUND
  Although genetic alterations in patients with advanced gastric cancer have been extensively studied, those in patients with intramucosal neoplasia (IMN) are still poorly understood.
  
  
  METHODS
  We evaluated genetic differences in 158 IMNs, including 51 low-grade dysplasias, 58 high-grade dysplasias (HGDs), 30 intramucosal cancers (IMCs), and 19 mixed tumors (composed of IMC and HGD within the same tumor), using PCR-based microsatellite analysis [allelic imbalance (AI) and microsatellite instability (MSI)]. We classified the DNA methylation status as a hypermethylated epigenome, a moderately methylated epigenome, or a hypomethylated epigenome. In addition, p53 overexpression, β-catenin nuclear localization, and mucin expression were also examined.
  
  
  RESULTS
  From cluster analysis, the IMNs examined were categorized into four subgroups as follows. Tumors in subgroup 1 were characterized by MSI-high status, a hypermethylated epigenome, and loss or reduction of expression of MLH-1. Tumors in subgroup 2 showed a mixed pattern consisting of AI and MSI. In contrast, tumors in subgroup 3, which showed accumulation of multiple AIs, were closely associated with HGD, IMC, or mixed tumor and exhibited nuclear expression of β-catenin. Tumors in subgroup 4, which were generally low-grade dysplasias, exhibited a low frequency of AIs and no MSI. Although the mucin phenotype was not correlated with any subgroup, expression of mucin was associated with some subgroups. Overexpression of p53 was common in all subgroups.
  
  
  CONCLUSIONS
  The approach described herein was useful for studying genetic differences in IMNs. In addition, we suggest that stratification of genetic differences may help to identify genetic molecular profiles in IMNs.
authors.affiliation: Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 19-1, Morioka, 020-8505, Japan. tsugai@cocoa.ocn.ne.jp.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sugai
authors.affiliation: Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 19-1, Morioka, 020-8505, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Sugimoto
authors.affiliation: Department of Pharmacodynamics and Molecular Genetics, School of Pharmacy, Iwate Medical University, Morioka, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Habano
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Endoh
authors.affiliation: Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 19-1, Morioka, 020-8505, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Eizuka
authors.affiliation: Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 19-1, Morioka, 020-8505, Japan.
authors.forename: Koudai
authors.initials: K
authors.lastname: Tsuchida
authors.affiliation: Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Yamamoto
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kawasaki
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
authors.forename: Syunichi
authors.initials: S
authors.lastname: Yanai
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D000069916:Endoscopic Mucosal Resection; D005260:Female; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor
keywords: Allelic imbalance; Cluster analysis; Early gastric cancer; Methylation; Microsatellite instability