TTF-1 Is a Sensitive and Specific Immunohistochemical Marker for Autoimmune Gastritis

Autoimmune gastritis (AIG) is an inflammatory disorder that leads to corpus-restricted mucosal atrophy and is associated with the formation of well-differentiated neuroendocrine tumors and, possibly, gastric adenocarcinoma. The early histologic findings of disease are not specific, and the diagnosis may require correlation with autoantibody serology. Recent evidence demonstrated the upregulation of lung differentiation genes in AIG. Here, we assess the expression of TTF-1, a marker of lung differentiation, in 75 biopsies of AIG, 36 biopsies of multifocal atrophic gastritis (MAG), 29 biopsies of Helicobacter pylori gastritis, 10 biopsies of reactive gastropathy, and 10 normal gastric biopsies. TTF-1 was expressed in metaplastic mucinous glands in 52 (69.3%) corpus biopsies of AIG, with most showing at least moderate-intensity (2+) staining. TTF-1 staining was frequently observed in biopsies with partial atrophy (75%) and in those without intestinal metaplasia (66.7%) or enterochromaffin-like (ECL) cell hyperplasia (66.7%). Two (5.6%) corpus biopsies with MAG demonstrated focal weak (1+) TTF-1 expression. ECL cells and antral mucosa were consistently negative for TTF-1. Staining was absent in all other study groups. The sensitivity and specificity of TTF-1 for AIG were 69.3% and 97.7%, respectively. When at least moderate-intensity staining (2+) was considered positive, TTF-1 was 61.3% sensitive and 100% specific for AIG. These findings demonstrate that immunohistochemistry for TTF-1 can be used to confirm the diagnosis of AIG, particularly in the absence of typical histologic features of established disease, and that it may reduce the need for confirmatory serologic tests in the earlier histologic phases of disease.