[Molecular pathology of gastric cancer].

Gastric cancer is one of the most common cancers worldwide. In recent decades, major advancements in the understanding of the epidemiology, pathology and pathogenesis of gastric cancer have been witnessed. Infections with Helicobacter pylori or Epstein-Barr virus, dietary and lifestyle factors contribute to the risk of developing gastric cancer. With respect to pathogenesis at least three distinct types of gastric cancer exist, (1) proximal, (2) distal diffuse and (3) distal non-diffuse types. Genetic and epigenetic alterations are related to oncogene mutations and tumor suppressor gene inactivation. Canonical oncogenic pathways such as the WNT/β-catenin signaling pathway are de-regulated in gastric cancer. Hereditary and familial type gastric cancers are currently linked to CDH1 gene mutations and various genetic polymorphisms determining disease susceptibility. Molecular subtypes of gastric cancer have been identified which separate diffuse from intestinal type gastric cancer and are not entirely congruent with the histopathological phenotype according to Laurén but may influence chemosensitivity. Putative cancer stem cell markers of gastric cancer have been found (e.g. ADAM17, CD133, FZD7, LGR5) and correlate with patient prognosis. Thus, molecular phenotyping of gastric cancer is still in its infancy and the search for novel diagnostic, prognostic and predictive biomarkers continues.