Spasmolytic Polypeptide-Expressing Metaplasia and Intestinal Metaplasia: Time for Reevaluation of Metaplasias and the Origins of Gastric Cancer

Focal early lesions for SPEM induction. (A) Diastase resistant-PAS (DR-PAS) staining of a section of human fundic mucosa showing the focal development of SPEM in a single gland unit (*). Note that in comparison with the carmine staining of surface cells, SPEM staining with DR-PAS is characteristically more reddish pink. (B) TFF2 immunostaining staining with horseradish peroxidase secondary antibody staining and DAB (brown) chromagen showing a single gland unit with SPEM (*) surrounded by normal glands with TFF2-staining of mucous neck cells. (C, D) Dual staining for TFF2 (red, alkaline phosphatase secondary antibody, and Vector red chromagen) and H/K-ATPase (brown DAB staining) staining of parietal cells showing the presence of 1 SPEM gland in the fundic mucosa.

Compound glands containing SPEM and intestinal metaplasia. (A) Dual Alcian blue and PAS staining of a human fundic specimen showing compound glands with Alcian blue staining intestinal metaplasia in more luminal cells and PAS-staining SPEM at the bases of glands. (B) Dual Muc2 (brown) and TFF2 (red) immunostaining of a section of fundic mucosa showing glands with Muc2-immunoreactive intestinal metaplasia surmounting TFF2-staining SPEM. (C, D) Serial sections of fundic mucosa from a resection specimen showing in C dual immunostaining for Ki67 (brown nuclei) and TFF2 (red) and in D dual immunostaining for Ki67 and Muc2 (red). Whereas Ki67 staining nuclei can be seen in scattered SPEM cells, the majority of Ki67-staining cells nuclei are seen in Muc2-immunoreactive cells at the interface between SPEM and intestinal metaplasia.

A revised model for the evolution of metaplasia in the stomach. Loss of parietal cells leads to evolution of SPEM at the bases of glands from transdifferentiation of chief cells. With continuing chronic inflammation, intestinal metaplasia develops within the luminal aspect of SPEM glands. Over time, intestinal metaplasia comes to dominate over SPEM in metaplastic mucosa. In remains to be determined whether gastric cancer arises form SPEM or from proliferative intermediates generated during the further differentiation of SPEM into intestinal metaplasia.