Aberrant p16(INK4A) and DPC4/Smad4 expression in intraductal papillary mucinous tumours of the pancreas is associated with invasive ductal adenocarcinoma.
Andrew V. Biankin,Sandra A. Biankin,James G. Kench,Adrienne Morey,C.-S. Lee,Darren R. Head,Robert P. Eckstein,Thomas B. Hugh,Susan Henshall,R. L. Sutherland +9 more
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Aberrant protein expression of these cell cycle regulatory genes in IPMT and pancreatic intraepithelial neoplasia in the current model of pancreatic cancer progression suggest similarities in their development and may also represent the subsequent risk of invasive carcinoma.Abstract:
Background and aims: Intraductal papillary mucinous tumours (IPMT) of the pancreas constitute a unique pathological entity with an overall incidence of associated invasive malignancy of 20%. The malignant potential of an individual IPMT cannot be accurately predicted. Preoperative estimation of the risk of associated invasive malignancy with IPMT would be of significant clinical benefit. As aberrations in cell cycle regulatory genes are associated with the progression of precursor pancreatic ductal lesions to invasive adenocarcinoma, we examined expression of key cell cycle regulatory genes in the cyclin D1/retinoblastoma pathway and the transforming growth factor β/Smad4 signalling pathway in a cohort of patients with surgically resected IPMT. Methods: Sections of formalin fixed paraffin embedded pancreatic tissue from a cohort of 18 patients with IPMT were examined using immunohistochemistry for protein expression of cell cycle regulatory genes p16 INK4A , p21 CIP1 , p27 KIP1 , cyclin D1, pRb, and p53, as well as the cell signalling molecule Smad4. A comparison of expression levels was made between adenoma/borderline IPMT (10 patients) and intraductal papillary mucinous carcinoma (IPMC) (eight patients, four of whom harboured invasive carcinoma). Statistical analysis was performed using the χ 2 and Fisher9s exact tests. Results: Aberrant expression of the proteins examined increased in frequency from adenoma/borderline IPMT to IPMC. Specifically, there was a significantly greater incidence of loss of p16 INK4A expression in IPMC: 8/8 lesions (100%) compared with 1/10 (10%) adenoma/borderline IPMT (p Conclusions: These data indicate that loss of p16 INK4A and Smad4 expression occur more frequently in IPMC alone, or with associated invasive carcinoma, compared with adenoma/borderline IPMT. Aberrant protein expression of these cell cycle regulatory genes in IPMT and pancreatic intraepithelial neoplasia in the current model of pancreatic cancer progression suggest similarities in their development and may also represent the subsequent risk of invasive carcinoma.read more
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An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms
Ralph H. Hruban,Kyoichi Takaori,David S. Klimstra,N. Volkan Adsay,Jorge Albores-Saavedra,Andrew V. Biankin,Sandra A. Biankin,Carolyn C. Compton,Noriyoshi Fukushima,Toru Furukawa,Michael Goggins,Yo Kato,Günter Klöppel,Daniel S. Longnecker,Jutta Lüttges,Anirban Maitra,G. Johan A. Offerhaus,Michio Shimizu,Suguru Yonezawa +18 more
TL;DR: The purpose of this meeting was to define an international acceptable set of diagnostic criteria for PanINs and IPMNs and to address a number of ambiguities that exist in the previously reported classification systems for these neoplasms.
Journal ArticleDOI
Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study
Asif Khalid,Maliha Zahid,Sydney D. Finkelstein,Julia K. Leblanc,Neeraj Kaushik,Nuzhat A. Ahmad,William R. Brugge,Steven A. Edmundowicz,Robert H. Hawes,Kevin McGrath +9 more
TL;DR: Elevated amounts of pancreatic cyst fluid DNA, high-amplitude mutations, and specific mutation acquisition sequences are indicators of malignancy; the presence of a k-ras mutation is also indicative of a mucinous cyst.
Journal ArticleDOI
Targeted next-generation sequencing of cancer genes dissects the molecular profiles of intraductal papillary neoplasms of the pancreas
Eliana Amato,Marco Dal Molin,Marco Dal Molin,Andrea Mafficini,Jun Yu,Giuseppe Malleo,Borislav Rusev,Matteo Fassan,Davide Antonello,Yoshihiko Sadakari,Paola Castelli,Giuseppe Zamboni,Anirban Maitra,Roberto Salvia,Ralph H. Hruban,Claudio Bassi,Paola Capelli,Rita T. Lawlor,Michael Goggins,Aldo Scarpa +19 more
TL;DR: Using next‐generation sequencing to detect cyst fluid mutations has the potential to improve the diagnostic and prognostic stratification of pancreatic cystic neoplasms.
Journal ArticleDOI
Precursors to Invasive Pancreatic Cancer
TL;DR: This review will address some of the recent diagnostic controversies for these lesions, in particular features that distinguish IPMNs from PanIN lesions and the potential clinical impact of recognizing these precursor lesions in the context of early detection of pancreatic cancer.
Journal ArticleDOI
Intraductal neoplasms of the pancreas.
TL;DR: Progress in genetic sequencing of pancreatic neoplasms and the identification of specific genetic mutations also holds promise for the future development of novel gene-based diagnostic tests in intraductal neoplasm of the pancreas that might even be used in preoperative conditions.
References
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Cancer Cell Cycles
TL;DR: Genetic alterations affecting p16INK4a and cyclin D1, proteins that govern phosphorylation of the retinoblastoma protein and control exit from the G1 phase of the cell cycle, are so frequent in human cancers that inactivation of this pathway may well be necessary for tumor development.
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