Incomplete Intestinal Metaplasia as a High-Risk Clinical Phenotype in Gastric Carcinogenesis: Implications for...

Gastric cancer remains a leading cause of cancer-related mortality worldwide, underscoring the critical need for effective prevention through the management of precancerous lesions. Gastric intestinal metaplasia (GIM) is a key precursor, with its incomplete subtype (IIM) conferring a substantially higher risk of malignant progression compared to complete intestinal metaplasia (CIM). However, IIM is not merely a static histological variant but represents a dynamic, transitional epithelial state of mixed gastric and intestinal differentiation, driven by chronic inflammation. Its accurate identification and clinical management pose significant challenges.

This review synthesizes current evidence on IIM as a high-risk transitional phenotype in gastric carcinogenesis. We detail its cellular origins, primarily from spasmolytic polypeptide-expressing metaplasia (SPEM) via chief cell reprogramming (paligenosis), and its characteristic hybrid molecular signature. Diagnostically, definitive subtyping relies on histochemical staining (e.g., AB-PAS), as conventional endoscopy and histology lack sufficient precision, highlighting a barrier to routine risk stratification. Epidemiologically, IIM is associated with a 4- to 11-fold increased risk of gastric cancer compared to CIM. While Helicobacter pylori eradication may induce partial regression, patients with IIM retain a significant residual cancer risk, necessitating ongoing surveillance. Emerging endoscopic techniques (e.g., narrow-band imaging) and molecular biomarkers (including DMBT1, AQP5, TROP2, and OLFM4) show promise for improving in vivo detection and risk assessment, with combinatorial biomarker strategies potentially better capturing IIM's hybrid phenotype. Current classification systems have limitations, including the frequent coexistence of subtypes and a lack of validated biomarkers for precise risk stratification.

1、IIM is a biologically unstable, transitional lesion with a markedly elevated risk of progression to gastric adenocarcinoma, warranting its distinction from CIM in clinical practice. 2、 Reliance on specialized pathology for diagnosis limits widespread risk stratification, creating an urgent need for reliable endoscopic predictors and validated molecular biomarkers. 3、Even after successful H. pylori eradication, patients with IIM require long-term endoscopic surveillance due to persistent cancer risk. Future strategies must integrate IIM subtyping into personalized surveillance protocols to enhance gastric cancer prevention.