Histogenesis of gastric foveolar metaplasia following duodenal ulcer: a definite reparative lineage of Brunner's gland

Abstract

Aims: We aimed to clarify the histogenesis of gastric metaplasia in the duodenal mucosa, particularly in association with a reparative lineage of Brunner's glands.

Methods and results: Using immunohistochemical methods with recently developed antimucin monoclonal antibodies (mAbs) that distinguish foveolar and deep mucins of the gastric type, as well as mAb MIB-1, the histogenesis of gastric metaplasia was investigated in the duodenal wall of 20 surgically resected specimens. In duodenal ulcers extending into Brunner's glands with destruction of the muscularis mucosae, proliferating cells positive for MIB-1 were scattered in Brunner's glands. Interestingly, a group of proliferating cells was often seen next to the ulcerated surface. These cells were also positive for M1 (gastric-foveolar type mucin) but negative for M2 (deep gastric and Brunner glands' mucin). In regenerating ducts through granulation tissue, the proliferating cell zone was elongated, above which foveolar-type cells positive for M1 but negative for M2 were detected, indicating that the G-zone is newly established in Brunner's glands at the floor of an ulcer to produce gastric-foveolar cells. Subsequently, an organoid growth of the normal stomach mucosa is completed in the duodenum.

Conclusions: This study indicates a possible histogenetic pathway of gastric metaplasia in close association with a reparative lineage of Brunner's glands, suggesting that the occurrence of the gastric-foveolar type epi-thelium is not a simple expansion of Brunner's duct but a true metaplasia.