Cathepsin E is a marker of gastric differentiation and signet-ring cell carcinoma of stomach: a novel suggestion on gastric tumorigenesis

Gastric cancer (GC) presents various histological features, though the mechanism underlying its diversity is seldom elucidated. It is mainly classified into well differentiated tubular adenocarcinoma (tub1), moderately differentiated tubular adenocarcinoma (tub2), poorly differentiated adenocarcinoma (por), signet-ring cell carcinoma (sig), mucinous adenocarcinoma (muc), and papillary adenocarcinoma (pap). By screening, we found cathepsin E (CTSE) expresses universally in sig-type, occasionally in por-type, and rarely in tub1/tub2-type GC cell lines. In surgically-resected specimens, CTSE was immunostained in 50/51 sig-type (98.0%), 3/10 tub1-type (30.0%), 7/18 tub2-type (38.9%), 15/26 por-type (57.7%), 4/10 pap-type (40.0%), and 0/3 muc-type (0.0%) GC. In endoscopically-resected specimens, 6/7 sig-type (85.7%), 7/52 tub1-type (13.7%), 5/12 tub2-type (41.7%), 2/7 pap-type (28.6%) GC and 0/6 adenoma (0.0%) expressed CTSE. For non-malignant tissues, CTSE is universally expressed in normal fundic, pyloric, and cardiac glands of stomach, but hardly in other digestive organs. In the precancerous intestinal metaplasia of stomach, CTSE is mostly observed in mixed gastric-and-intestinal type and deficient in solely-intestinal type. CTSE expression is positively correlated with gastric marker MUC5AC (p