title: HIP/PAP, a member of the reg family, is expressed in glucagon-producing enteropancreatic endocrine cells and tumors.
abstract: Hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP) protein, a member of the reg family, is constitutively expressed by some specialized epithelial cell subsets in the digestive tract and the pancreas. We performed a detailed analysis of the expression of HIP/PAP protein in normal digestive endocrine cells according to their localization, lineage, and differentiation stage, and in digestive endocrine tumors according to their site of origin and hormonal profile. In both adult and fetal normal tissues, HIP/PAP expression was detected only in endocrine cells of the small intestine, ascending colon, and pancreas. Two different expression patterns were identified: (a) a strong cytoplasmic labeling observed in the endocrine cells of the digestive mucosa and the outer rim of Langerhans islets specialized in the synthesis of glucagon and glucagon-like peptides; (b) a weak cytoplasmic immunoreactivity observed in the other pancreatic endocrine cell populations. HIP/PAP expression was detected in 36 of the 184 cases of digestive endocrine tumors examined; 32 of these cases (89%) were pancreatic. The 2 patterns observed in the normal state were retained: (a) a strong labeling was observed in 5% to 100% of tumor cells in 26 tumors, all expressing glucagon or glucagon-like peptides; (b) a weak labeling was present in 10 tumors, presenting various hormonal profiles. In conclusion, a strong expression of HIP/PAP is characteristic of glucagon-producing normal and neoplastic enteropancreatic endocrine cells. Our results lend further support to the concept that members of the reg family play regulatory roles in various endocrine cell populations and that their expression in endocrine cells is lineage-specific.
authors.affiliation: INSERM, U45, IFR62, Faculté Laennec, 69372 Lyon, France; Service Central d'Anatomie et Cytologie Pathologiques, Hôpital Edouard Herriot, 69437 Lyon, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Hervieu
authors.forename: Laurence
authors.initials: L
authors.lastname: Christa
authors.forename: Géraldine
authors.initials: G
authors.lastname: Gouysse
authors.forename: Raymonde
authors.initials: R
authors.lastname: Bouvier
authors.forename: Jean-Alain
authors.initials: JA
authors.lastname: Chayvialle
authors.forename: Christian
authors.initials: C
authors.lastname: Bréchot
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Scoazec
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004067:Digestive System Neoplasms / Q000378:metabolism* / Q000473:pathology; D004701:Endocrine Gland Neoplasms / Q000378:metabolism* / Q000473:pathology; D019858:Enteroendocrine Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005333:Fetus; D041981:Gastrointestinal Tract / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D005934:Glucagon / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D037181:Lectins, C-Type / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000073718:Pancreatitis-Associated Proteins
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D005934:Glucagon