Pepsinogen I- and H+/K+-ATPase-immunohistochemical Positivity in Endoscopically Resected Early Gastric Neoplasia

Abstract

Gastric adenocarcinoma of the fundic gland type (GAFG) has been recently classified by the World Health Organization (WHO), however, clinicopathologic features of pepsinogen I- or H+/K+-ATPase-positive gastric tumors remain unclear. Therefore, this study evaluates the frequency and clinicopathologic features of those tumors, using a tissue microarray block to identify pepsinogen I- or H+/K+-ATPase-positive tumors from 810 endoscopically resected, early gastric epithelial tumors. The frequency of pepsinogen I-positive lesions was 2.1%, and that of H+/K+-ATPase-positive lesions was 2.0%. Pepsinogen I- or H+/K+-ATPase positivity was not observed in undifferentiated-type tumors, while gastric tumors with morphologic similarity to fundic glands were positive for pepsinogen I- or H+/K+-ATPase. We divided pepsinogen I- or H+/K+-ATPase-positive gastric tumors into group A, with fundic gland-like structure, or group B, without fundic gland-like structure. The frequency of group A was 1.6%: 46.2% were positive only for pepsinogen I and 53.8% for H+/K+-ATPase and pepsinogen I. The frequency of group B was 1.5%: 25% were positive only for pepsinogen I, 8.3% for H+/K+-ATPase and pepsinogen I, and 66.7% only for H+/K+-ATPase. The 2 tumor groups differed in location and endoscopic features. Hematoxylin and eosin staining showed that group B had more exposed tumors to the surface, larger nuclei, and more background atrophy than group A. Immunostaining showed significantly higher positivity rates for MUC5AC, CD10, CDX2, and p53 expression, and a higher Ki-67 labeling score. Our results provide novel insights into the pathology of early gastric tumors with histologic or immunohistochemical evidence of fundic gland differentiation.