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.