Spasmolytic polypeptide-expressing metaplasia (SPEM) cell lineages can be an origin of gastric cancer

Intestinal-type gastric cancer arises in a field of precancerous metaplastic lineages. Two types of metaplastic glands are found in the stomachs of humans with the characteristics of pyloric metaplasia or intestinal metaplasia. While spasmolytic polypeptide-expressing metaplasia (SPEM) cell lineages have been identified in both pyloric metaplasia and incomplete intestinal metaplasia, it has been unclear whether SPEM lineages or intestinal lineages can give rise to dysplasia and cancer. A recent article published in The Journal of Pathology describes a patient with evidence of an activating Kras(G12D) mutation in SPEM that is propagated into adenomatous and cancerous lesions which manifest further oncogenic mutations. This case therefore supports the concept that SPEM lineages can serve as a direct precursor for dysplasia and intestinal-type gastric cancer. © 2023 The Pathological Society of Great Britain and Ireland.