Pathology of gastric cancer and its precursor lesions.

Gastric cancers are a histologically heterogenous group of neoplasms arising from unique epidemiologic and molecular backgrounds. There is accumulating evidence that the intestinal type of gastric adenocarcinoma develops through a multistep process beginning with chronic gastritis triggered primarily by Helicobacter pylori and progressing through atrophy, intestinal metaplasia, and dysplasia (intraepithelial neoplasia) to carcinoma. Loss of E-cadherin expression resulting from CDH1 gene alterations is the primary carcinogenetic event in hereditary diffuse gastric cancer. Proximal gastric adenocarcinomas likely result from either gastroesophageal reflux or H pylori gastritis. This article provides an update of the histologic, immunohistochemical, and molecular pathways of gastric cancer and its precursors.