Metaplasia and the Origins of Gastric Cancer—Implications for Screening and Surveillance

Gastric intestinal metaplasia (IM) is a key step in the development of intestinal‐type gastric cancer (GC) and a checkpoint for preventive strategies. The risk of progression to GC is highest for incomplete IM and extensive severe IM as classified by scoring systems such as operative link on gastric intestinal metaplasia (OLGIM) assessment, whereas the majority with mild or focal IM do not progress. Its pathogenesis is characterized by Helicobacter pylori ‐triggered chronic inflammation driving epithelial lineage reprogramming and CDX1/2 activation. IM clones develop and acquire early driver mutations (TP53, APC, and FBXW7), 8q/MYC gains, telomere attrition, and promoter hypermethylation, establishing a precancerous field, from which further evolution to dysplasia and cancer may occur. Recent preliminary data have suggested the possibility of reversing IM by MEK inhibition to induce mucosal reprogramming. Clinical management centers on H. pylori eradication, surveillance by high‐quality endoscopy and guided by risk stratification using OLGIM or endoscopic grading of gastric intestinal metaplasia (EGGIM). Future work should prospectively validate tissue and blood biomarkers, integrate image‐based risk scores into routine care, and test antiprogression and field‐modifying therapies in randomized trials. In conclusion, IM is an actionable checkpoint for cancer interception, and its finding in a patient should prompt the consideration of surveillance and preventive strategies to avert progression to GC.