title: Inactivation of the p16 (INK4A) tumor-suppressor gene in pancreatic duct lesions: loss of intranuclear expression.
abstract: Pancreatic adenocarcinoma develops from histologically identifiable intraductal lesions that undergo a series of architectural, cytological, and genetic changes. Limited genetic evidence recently suggested that the p16 gene plays a role in the progression of these "duct lesions." Duct lesions were identified in pancreata from 33 pancreaticoduodenectomies performed for infiltrating adenocarcinoma. All of these infiltrating adenocarcinomas were previously shown to contain alterations in the p16 gene or its promoter. Monoclonal and polyclonal anti-p16 antibodies were used for histological immunodetection. One hundred twenty-six duct lesions were identified. Nine (30%) of 30 flat, 4 (27%) of 15 papillary, 37 (55%) of 67 papillary with atypia, and 10 (71%) of 14 carcinoma in situ duct lesions showed loss of p16 expression. These included 30% of the flat lesions versus 53% of the nonflat lesions and 29% of the nonatypical lesions versus 58% of the atypical lesions. For both comparisons, the differences were statistically significant (P = 0.036 and P = 0.003, respectively). Loss of p16 expression occurs more frequently, but not exclusively, in higher-grade duct lesions. These data support the hypothesis that pancreatic duct lesions are neoplastic and that they represent the precursors of infiltrating adenocarcinoma. Immunohistochemical detection of p16 provides a new technology to study the genetic alterations in and stages of progression of large numbers of morphologically defined pancreatic duct lesions.
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Wilentz
authors.forename: J
authors.initials: J
authors.lastname: Geradts
authors.forename: R
authors.initials: R
authors.lastname: Maynard
authors.forename: G J
authors.initials: GJ
authors.lastname: Offerhaus
authors.forename: M
authors.initials: M
authors.lastname: Kang
authors.forename: M
authors.initials: M
authors.lastname: Goggins
authors.forename: C J
authors.initials: CJ
authors.lastname: Yeo
authors.forename: S E
authors.initials: SE
authors.lastname: Kern
authors.forename: R H
authors.initials: RH
authors.lastname: Hruban
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D016147:Genes, Tumor Suppressor; D019942:Genes, p16; D006801:Humans; D010179:Pancreas / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology