title: Gastric cancer carcinogenesis and tumor progression.
abstract: BACKGROUND
  Gastric cancer (GC) remains one of the leading causes of cancer-related deaths worldwide, even though a decline has been observed in its incidence and the mortality rate in recent decades. Gastric carcinogenesis is a complex phenomena involving multiple epigenetic and genetic factors; several genetic, environmental and infectious agents interact causing a cumulative effect in the early steps of gastric carcinogenesis.
  
  
  METHODS
  The most commonly used classifications of GC are the World Health Organization (WHO) and the Laurén classifications which describes two main histological types, diffuse and intestinal, which have different clinicopathological characteristics. Diffuse cancer occurs more commonly in young patients, can be multifocal, is not often accompanied by intestinal metaplasia and can be hereditary, in which E-cadherin alteration plays a pivotal role. Intestinal type is more frequently observed in older patients and follows multifocal atrophic gastritis. This is usually accompanied by intestinal metaplasia and leads to cancer via dysplasia, and thus intestinal metaplasia is considered a dependable morphological marker for GC risk. Intestinal adenocarcinoma predominates in the high-risk areas whereas the diffuse adenocarcinoma is more common in low-risk areas.
  
  
  CONCLUSIONS
  Classically, genetic instability and Helicobater pylori (H. Pylori) infection are often identified in intestinal GC. The great majority of GCs are sporadic and result from the cumulative effects of different environmental risk factors; smoking, alcohol consumption and dietary habits have been addressed as significant. H. Pylori infection and proinflammatory cytokine gene polymorphisms represent other features of this compound process that leads to the development of GC. Other molecular pathway well described in GC is microsatellite instability (MSI) that related with specific clinic-pathological features.
  
  
  CONCLUSIONS
  In this review we focused on the role of H. Pylori infection, MSI and alterations of CDH1 (E-Cadherin) gene.
authors.affiliation: Dipartimento di Patologica Umana ed Oncologica, Sezione di Chirurgia Generale e Oncologica, Università di Siena, Italia.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corso
authors.forename: Raquel
authors.initials: R
authors.lastname: Seruca
authors.forename: Franco
authors.initials: F
authors.lastname: Roviello
mesh_terms: D015820:Cadherins / Q000235:genetics; D018450:Disease Progression; D006801:Humans; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology
chemical_list: D015820:Cadherins