Gastric adenocarcinoma of the fundic gland type shares common genetic and phenotypic features with pyloric gland adenoma.

Gastric adenocarcinoma of the fundic gland type (GAFG) and pyloric gland adenoma (PGA) have recently been recognized as rare types of neoplasia. We performed comparative immunohistochemical and genetic analyses of 3 GAFGs and 12 PGAs. All of the 3 GAFGs were diffusely positive for pepsinogen-I, MIST1 and MUC6, indicating the predominantly chief cell/mucous neck cell differentiation of these tumors. A small number of H.K-ATPase-positive parietal cells were also scattered. PGAs invariably exhibited diffuse MUC6 and TFF2 expression, consistent with the pyloric gland differentiation of these tumors. Ten of the 12 PGAs also unexpectedly exhibited focal expression of pepsinogen-I and MIST1, suggesting that PGAs often show focal chief cell differentiation and phenotypically resemble mucous neck cells rather than pyloric glands. The mutation analyses revealed activating GNAS mutations, which have been reported to be frequently detected in PGAs, in two of the GAFGs. While GAFGs and PGAs are morphologically distinct lesions, our observations showed their partially overlapping immunohistochemical profiles and shared presence of GNAS mutations, in addition to their common occurrence in the fundic gland mucosa. Based on these observations, we suggest that both GAFGs and PGAs are closely related lesions characterized by a mucous neck cell/chief cell lineage phenotype.