title: Mucin gene expression in intraductal papillary-mucinous pancreatic tumours and related lesions.
abstract: Intraductal papillary-mucinous tumours (IPMTs) of the pancreas are heterogeneous proliferations characterized by a malignant potential. The molecular mechanisms underlying the tumourigenesis process are not well understood. Recently, it has been shown that IPMTs secreting the mucin antigen MUC2 have a better prognosis, but the complete pattern of MUC gene expression has not yet been established. The aims of this study were to evaluate the mucin gene expression in 57 IPMTs and eight related lesions surgically resected and to relate MUC gene expression to the histological diagnosis. In situ hybridization (ISH) was performed in 28 cases with probes specific for the MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6, and MUC7 genes. An immunohistochemical analysis was carried in all 65 cases and in 90 conventional ductal adenocarcinomas of the pancreas using MUC1, MUC2, and MUC5AC antibodies. IPMTs of adenoma (dysplasia) type exhibited high expression of MUC2 (93%), MUC5AC (97%), and, to a lesser extent, of MUC4 (71%), all of which were also observed in colloid carcinomas associated with IPMTs. In contrast, IPMTs with simple hyperplasia, intraductal oncocytic papillary neoplasms, and pyloric glandular adenomas exhibited little or no expression of MUC2. The mucin expression profile supports the existence of two types of invasive tumour associated with IPMTs: a colloid and an ordinary form. The latter shows a pattern similar to the conventional ductal adenocarcinomas with a loss of MUC2 and a gain of MUC1 and has a greater tendency to metastasize. In conclusion, the altered expression of mucin, characteristic of IPMT of adenoma type and of colloid carcinomas, may contribute to the better clinical outcome of these neoplasms, compared to conventional pancreatic ductal adenocarcinomas.
authors.affiliation: Services d'Anatomie Pathologique, Hôpital Cochin, Paris, France. benoitterris@hotmail.com
authors.forename: Benoît
authors.initials: B
authors.lastname: Terris
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dubois
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Buisine
authors.forename: Alain
authors.initials: A
authors.lastname: Sauvanet
authors.forename: Philippe
authors.initials: P
authors.lastname: Ruszniewski
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Aubert
authors.forename: Nicole
authors.initials: N
authors.lastname: Porchet
authors.forename: Anne
authors.initials: A
authors.lastname: Couvelard
authors.forename: Claude
authors.initials: C
authors.lastname: Degott
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Fléjou
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism; D055262:Mucin-2; D009077:Mucins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C524625:MUC2 protein, human; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D018396:Mucin-1; D055262:Mucin-2; D009077:Mucins; D009363:Neoplasm Proteins