Pancreatic digestive enzymes have rarely been reported in human nonpancreatic organs. We examined their expression in the epithelial cells of the nonpancreatic gastrointestinal organs, looking for pancreatic alpha-amylase, trypsin, chymotrypsin and pancreatic lipase. Western blotting, enzyme assay and pancreatic alpha-amylase mRNA were also used in selected specimens. In normal tissues, immunoreactivity of one or more of these enzymes was frequently noted in cells of the salivary glands, stomach, duodenum, large pancreatic ducts, extrahepatic bile ducts and gall bladder. The epithelium of the normal oesophagus, small intestine and colon were consistently negative for these enzymes. In pathologic tissues, immunoreactivity for one or more enzymes was present in epithelial cells of pleomorphic adenomas of the salivary glands, oesophageal squamous cell carcinoma, gastric adenoma and adenocarcinoma, pancreatic adenocarcinoma, cholecystitis, adenocarcinoma of the gall bladder and extrahepatic bile duct, and colon adenoma and adenocarcinoma. Western blotting showed a specific band of each enzyme in some specimens of normal stomach. In situ hybridization for pancreatic alpha-amylase mRNA showed specific signals in the normal stomach, but not in the normal colon. Reverse transcriptase polymerase chain reaction analysis for pancreatic alpha-amylase mRNA revealed specific signals in the normal stomach. Enzyme assay revealed that the stomach and gall bladder showed these activities. The data suggest that pancreatic digestive enzymes are produced by several epithelial cell types of the nonpancreatic gastrointestinal organs, that the organs positive for pancreatic enzyme have a common cell lineage, and that neoplasms continue to express or neoexpress these enzymes after neoplastic transformation.

Conclusions-These results strongly suggest that biliary epithelia of larger intrahepatic ducts produce pancreatic a-amylase, lipase, and trypsin, and that these enzymes are secreted into the lumina of intrahepatic bile ducts.( 7 Clin Pathol 1994;47:924-927)

We investigated whether carbohydrate antigens on cholangitis, 2,4 in which the proliferated peribiliary biliary glycoproteins and carcinoembryonic antigen glands secrete large amounts of acid (sialylated and (CEA) are related to hepatolithiasis. CEA, ABO, and sulfated) or neutral mucin into the biliary lumen. 4 Most Lewis blood group-related antigens, as well as sialylintrahepatic calculi consist of calcium-bilirubinate Tn antigen in hepatic bile, were analyzed by Western (brown pigment) stones. 4,5 Bacterial infection, bile stablotting in samples from 12 patients with hepatolithiasis sis, and an alteration of the bile composition are and 37 with other biliary diseases (choledocholithiasis, thought to be responsible for the nucleation, formation, 13; cholecystolithiasis, 5; acute cholecystitis, 2; choland maturation of intrahepatic calculi. 6,7 In addition, angiocarcinoma, 5; common bile duct carcinoma, 4; panthe increased mucin production and secretion from the creatic carcinoma, 6; and metastatic carcinoma of liver, bile ducts may play an important role in the develop-2). CEA was positive on mucinous glycoprotein in six patients (50%) with hepatolithiasis and one case (17%) ment of intrahepatic calculi. 4,5,8 Biliary mucin, particuwith pancreatic carcinoma. CEA was also positive on a larly sulfated, reportedly promotes the formation of calglycoprotein of approximately 200 kd in eight patients cium-bilirubinate stones. 4,7 Histochemically, these (67%) with hepatolithiasis and two (33%) with pancreatic stones are composed of alternating multilayers of mucarcinoma. Lewis X was detected on the mucinous glycocin and pigment (calcium-bilirubinate) on their cut surprotein in almost all samples, as well as on glycoproteins face, suggesting that mucin bridges the pigment layers of approximately 180 kd in all hepatolithiasis samples and participates in the precipitation of calcium-biliruand approximately half of those from patients with other binate. 9 diseases. Sialyl-Tn antigen was detected on mucinousCarbohydrate antigens of glycoproteins, glycolipids, glycoprotein in four (80%) with cholangiocarcinoma, two and proteoglycans play an important role in cell-to-

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