Identification of a metaplastic cell lineage associated with human gastricadenocarcinoma

Metaplastic cell lineages arising in response to chronic injury are precurs ors for the evolution of dysplasia and adenocarcinoma. Although a subtype o f intestinal metaplasia has been associated with gastric adenocarcinoma, th e link between this lineage and the evolution of gastric adenocarcinoma has remained unclear. Wang et al (1998) have reported that an aberrant metapla stic cell lineage with morphological characteristics similar to Brunner's g lands of the duodenum develops in the fundic mucosa of mice infected with H elicobacter tells. This metaplastic lineage expresses the trefoil peptide s pasmolytic polypeptide (SP). Given the epidemiological association of Helic obacter species infection with gastric cancer, we hypothesized that this SP -expressing metaplastic (SPEM) lineage may represent a precursor to or appe ar commensurate with gastric adenocarcinoma. The SPEM lineage was present i n 68% of fundic biopsies from patients with fundic Helicobacter pylori-asso ciated gastritis, but was absent in biopsies of fundic mucosa from patients without H. pylori infection. In a review of archival samples from 22 resec ted gastric adenocarcinomas, we found the SPEM lineage in 91% of cases, typ ically located in mucosa adjacent to the carcinoma or areas of dysplasia. i mportantly, 59% of resections showed SP immunoreactivity within dysplastic cells. These data indicate a strong association of the SPEM lineage with bo th chronic H. pylori infection and gastric adenocarcinoma.