title: [Gastric cancer: histological type, histogenesis, and gene abnormalities].
abstract: The development and progression of gastric cancer involves a number of genetic and epigenetic abnormalities. The majority of differentiated adenocarcinomas arise from intestinal metaplastic mucosa and exhibit structurally altered tumor suppressor genes (suppressor pathway), typified by p53, which is inactivated via the classic two-hit mechanism, i.e. loss of heterozygosity (LOH) and mutation of the remaining allele. LOH at certain chromosomal loci accumulates during tumor progression. Approximately 20% of differentiated adenocarcinomas show evidence of mutator pathway tumorigenesis due to hMLH1 inactivation via hypermethylation of promoter CpG islands, and exhibit high-frequency microsatellite instability (MSI-H) (mutator pathway). In contrast, undifferentiated carcinomas rarely exhibit structurally altered tumor suppressor genes. For instance, while methylation of E-cadherin in native gastric mucosa is often observed in undifferentiated carcinomas, mutation of this gene is generally associated with the progression from differentiated adenocarcinomas to undifferentiated carcinomas. Hypermethylation of a number of tumor suppressor and tumor-related genes can be detected in both differentiated adenocarcinomas and undifferentiated carcinomas at varying frequencies. Promoter demethylation of specific genes, such as MAGE and Synuclein gamma, can occur during the progressive stages of both histological types, and is associated with patient prognosis. Thus, the molecular pathways of gastric carcinogenesis are dependent on histological background, and specific genetic abnormalities can be used for risk assessment, diagnosis, and prognosis.
authors.affiliation: Dept. of Pathology and Laboratory Medicine, Yamagata Prefectural Central Hospital.
authors.forename: Gen
authors.initials: G
authors.lastname: Tamura
mesh_terms: D002454:Cell Differentiation; D006801:Humans; D018895:Microsatellite Repeats; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*