Gastric Intestinal Metaplasia in Mucosa Adjacent to Gastric Cancers Is Rarely Associated With the Aneuploidy That Is Characteristic of Gastric Dysplasia or Cancer

Most gastric cancers (GCs) are thought to develop via gastric intestinal metaplasia (GIM)-dysplasia-carcinoma pathway. Patients with extensive and/or incomplete GIM have been reported to have a higher risk of GC. GIM can also display dysplasia-like cytoarchitectural atypia limited to the bases of gastric pits without surface involvement. However, only a small proportion of GIM patients will develop gastric neoplasia, and it remains questionable if GIM is a direct precursor. A cohort of 82 GC patients with GIM who underwent gastrectomy were analyzed. DNA flow cytometry was performed on 109 GIM samples (including 88 predominantly complete GIM and 21 predominantly incomplete GIM subclassified based on morphology) obtained from adjacent mucosa of the 82 GCs. Only 2 (2%) of the 109 GIM samples demonstrated aneuploidy, both from 2 minority patients (Asian and Hispanic) with limited and complete GIM and no cytoarchitectural atypia. The remaining 107 GIM samples showed mild to focally moderate basal gland (metaplastic) atypia limited to the bases of gastric pits, but they all demonstrated normal DNA content regardless of anatomic location, histologic GIM subtype, or varying degrees of basal gland atypia. In conclusion, the vast majority of the GIM samples (98%) lack the aneuploidy that is characteristic of gastric dysplasia or cancer. This indicates that aneuploidy usually occurs after the development of gastric dysplasia rather than at the stage of GIM. The finding also suggests that the presence of GIM alone may not be sufficient to suggest an increased risk for GC and that the inclusion of other high-risk features (ie, extensive GIM, dysplasia, racial minorities, and/or family history of GC in a first-degree relative) and/or aneuploidy ought to play a role in the selection of GIM patients who may warrant endoscopic surveillance. Finally, GIM with mild to focally moderate basal gland atypia is likely to represent metaplastic atypia in most cases.