title: Clinicopathological and molecular alterations in early gastric cancers with the microsatellite instability-high phenotype.
abstract: The relevance of the clinicopathological and molecular features of early gastric cancers (EGCs) having the microsatellite instability (MSI)-high phenotype has not been clearly defined in sporadic gastric carcinogenesis. Here, we examined the clinicopathological and molecular characteristics of EGC according to MSI status in 330 patients with EGC (intestinal-type adenocarcinoma). Tumors were classified as MSI-high (45 cases), MSI-low (9 cases), or microsatellite stable (MSS; 276 cases). The specimens were examined using a combination of polymerase chain reaction (PCR)-microsatellite assays and PCR-pyrosequencing to detect chromosomal allelic imbalances in multiple cancer-related chromosomal loci, MSI, gene mutations (KRAS and BRAF) and methylation status [high methylation epigenome (HME), intermediate methylation epigenome and low methylation epigenome]. In addition, the expression levels of various target proteins were examined using immunohistochemistry. Interestingly, EGC with the MSI phenotype showed distinct papillary features. The expression of gastric mucin was more frequent in EGC with the MSI phenotype, while p53 overexpression was common in EGCs, irrespective of MSI status. The frequency of HME was significantly higher in EGCs with the MSI phenotype than in EGCs with the MSS phenotype. Although there was a low frequency of allelic imbalance in EGCs with the MSI phenotype, some markers of allelic imbalance were more frequently detected in EGCs with the MSI-high phenotype than in EGCs with the MSS phenotype. KRAS and BRAF mutations were rare in EGCs. Thus, the MSI phenotype in EGC is a major precursor lesion in gastric cancer and is characterized by distinct clinicopathological and molecular features.
authors.affiliation: Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Sugimoto
authors.affiliation: Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sugai
authors.affiliation: School of Medicine, Iwate Medical University, Morioka, Japan.|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, Sapporo Medical University, Chuoh-ku Sapporo, Hokkaido, Japan.|Department of Internal Medicine, Sapporo Medical University, Chuoh-ku Sapporo, Hokkaido, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Endoh
authors.affiliation: Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Eizuka
authors.affiliation: Department of Biochemistry, Sapporo Medical University, Chuoh-ku Sapporo, Hokkaido, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Yamamoto
authors.affiliation: Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Uesugi
authors.affiliation: Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ishida
authors.affiliation: Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kawasaki
authors.affiliation: Division of Gastroenterology, Sapporo Medical University, Chuoh-ku Sapporo, Hokkaido, Japan.|Department of Internal Medicine, Sapporo Medical University, Chuoh-ku Sapporo, Hokkaido, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Biochemistry, Sapporo Medical University, Chuoh-ku Sapporo, Hokkaido, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*
keywords: allelic imbalance; early gastric cancer; methylation; microsatellite instability; papillary adenocarcinoma