Slow moving proteinase in gastric cancer and its relationship to pepsinogens I and II. An immunohistochemical study.

Slow-moving proteinase (SMP), pepsinogen I (PG I), and pepsinogen II (PG II) are aspartic proteinases normally found in gastric mucosa. Because of differences in their cellular origins, normal gastric epithelial cells can be phenotyped by immunohistochemical staining with a panel of antisera to each proteinase. In this study, we determined aspartic proteinase phenotypes of malignant cells in 74 cases of gastric cancer by immunohistochemical staining with rabbit antiserum to human SMP, PG I, and PG II. Of the 74 cancers, 20 were histologically of the diffuse type and 54 were of the intestinal (or mixed) type. Intestinal metaplasia was characterized by the presence of SMP (but not PG I or PG II) in absorptive epithelial cells. SMP was found in 40 (54%) of the cancers (vs 31% for PG II and only 5% for PG I) and in both the intestinal and diffuse types. Of the 40 SMP-positive cancers, 14 also expressed PG II. In the latter tumors, staining of adjacent sections revealed that some malignant cells expressed only SMP or only PG II, whereas others expressed both proteinases. Overall, 49 (66%) of the cancers contained cells with proteinase phenotypes characteristic of cells in nonmalignant gastric mucosa and 23% contained cells with proteinase phenotypes characteristic of more than one cell type. The results indicate that both intestinal- and diffuse-type gastric cancers often differentiate to cell types that produce aspartic proteinases and that about one fourth contain a heterogeneous population of malignant cells.