| [ Summary ] |
Gastric adenocarcinoma of the fundic gland type (GAFG) has recently been proposed as a new, rare variant of gastric adenocarcinoma. GAFG has distinct clinicopathological, immunohistochemical, and endoscopic features. GAFG is defined by positive immunohistochemical staining for pepsinogen‒I (a marker of chief cells) and/or H+/K+‒ATPase (a marker of parietal cells) and is not associated with the Helicobacter pylori (H. pylori) infection. With regard to biological behavior, GAFG is considered to be less aggressive because it exhibits low cellular atypia, no lymphovascular invasion, low proliferative activity, a lack of p53 protein overexpression, and a good prognosis. We also analyzed the molecular events of GAFG, and suggested that a progression of GAFG might be associated with GNAS mutations and the Wnt/β-catenin signaling pathway. Recently, many cases of an aggressive variant of GAFG with high cellular atypia have been discovered. One of the variants exhibited differentiation toward gastric foveolar epithelium in addition to fundic gland differentiation, and was designated as gastric adenocarcinoma of fundic gland mucosal type (GAFGM). GAFGM may be an appropriate nomenclature for an aggressive variant of GAFG with a foveolar differentiation. Further studies are needed to clarify the natural history and clinicopathological features of GAFG, including GAFGM, by assessing the long‒term outcome and new classification based on grade of atypism and cell differentiation. |