title: MUC4 expression increases progressively in pancreatic intraepithelial neoplasia.
abstract: Pancreatic adenocarcinoma is believed to develop from histologically identifiable intraductal lesions known as pancreatic intraepithelial neoplasias (PanINs) that undergo a series of architectural, cytologic, and genetic changes, a progression model similar to the adenoma-carcinoma sequence in the colon. The apomucin MUC4 has been implicated in invasive pancreatic adenocarcinoma. MUC4 expression is not detectable at the RNA level in normal pancreas but is detectable at high levels in invasive pancreatic adenocarcinoma. We documented the pattern of expression of MUC4 in PanINs by studying a series of 71 PanIN lesions immunohistochemically using a new monoclonal antibody to MUC4. Five (17%) of 30 PanIN-1 lesions, 10 (36%) of 28 PanIN-2 lesions, 11 (85%) of 13 PanIN-3 lesions, and 25 (89%) of 28 invasive adenocarcinomas labeled with the MUC4 antibody used in the study. In addition, afew nonneoplastic lesions labeled with the MUC4 antibody, including reactive ducts in chronic pancreatitis, atrophic ducts filled with inspissated secretions, and ducts showing squamous metaplasia. Our data help establish the patterns of MUC4 expression in neoplastic precursors in the pancreas and add further support to the progression model for pancreatic adenocarcinoma.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Swartz
authors.forename: Surinder K
authors.initials: SK
authors.lastname: Batra
authors.forename: Grish C
authors.initials: GC
authors.lastname: Varshney
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hollingsworth
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Yeo
authors.forename: John L
authors.initials: JL
authors.lastname: Cameron
authors.forename: Robb E
authors.initials: RE
authors.lastname: Wilentz
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: Pedram
authors.initials: P
authors.lastname: Argani
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002278:Carcinoma in Situ / Q000378:metabolism* / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D018450:Disease Progression; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007150:Immunohistochemistry; D055264:Mucin-4; D009077:Mucins / Q000378:metabolism*; D010183:Pancreatic Ducts / Q000033:anatomy & histology / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C524658:MUC4 protein, human; D055264:Mucin-4; D009077:Mucins