title: Molecular, morphological and survival analysis of 177 resected pancreatic ductal adenocarcinomas (PDACs): Identification of prognostic subtypes.
abstract: Pancreatic ductal adenocarcinoma (PDAC) has generally a poor prognosis, but recent data suggest that there are molecular subtypes differing in clinical outcome. This study examines the association between histopathologic heterogeneity, genetic profile, and survival. Tumor histology from 177 resected PDAC patients with follow-up data was subclassified according to predominant growth pattern, and four key genes were analyzed. PDACs were classified as conventional (51%), combined with a predominant component (41%), variants and special carcinomas (8%). Patients with combined PDACs and a dominant cribriform component survived longer than patients with conventional or other combined PDACs. Genetic alterations in at least two out of four genes were found in 95% of the patients (KRAS 93%, TP53 79%, CDKN2A/p16 75%, SMAD4 37%). Patients with less than four mutations survived significantly longer (p = 0.04) than those with alterations in all four genes. Patients with either wildtype KRAS or CDKN2A/p16 lived significantly longer than those with alterations in these genes (p = 0.018 and p = 0.006, respectively). Our data suggest that the number of altered genes, the mutational status of KRAS and certain morphological subtypes correlate with the outcome of patients with PDAC. Future pathology reporting of PDAC should therefore include the KRAS status and a detailed morphological description.
authors.affiliation: Institute of Pathology, Technische Universität München, Munich, Germany.
authors.forename: Anna Melissa
authors.initials: AM
authors.lastname: Schlitter
authors.affiliation: Institute of Pathology, Technische Universität München, Munich, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Segler
authors.affiliation: Institute of Pathology, Technische Universität München, Munich, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Steiger
authors.affiliation: Department of Surgery, University Hospital Heidelberg, Germany.
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Michalski
authors.affiliation: Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Jäger
authors.affiliation: Institute of Pathology, Technische Universität München, Munich, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Konukiewitz
authors.affiliation: Institute of Pathology, Technische Universität München, Munich, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Pfarr
authors.affiliation: Institute of Pathology, University Hospital of Heidelberg, Heidelberg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Endris
authors.affiliation: Molecular Pathology South-Bavaria, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Bettstetter
authors.affiliation: Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Bo
authors.initials: B
authors.lastname: Kong
authors.affiliation: Institute of Pathology, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Ivonne
authors.initials: I
authors.lastname: Regel
authors.affiliation: The Royal Liverpool and Broadgreen University Hospitals, Prescot Street, Liverpool L7 8XP, United Kingdom.|Department of General-, Visceral- and Pediatric Surgery, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kleeff
authors.affiliation: Institute of Pathology, Technische Universität München, Munich, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Klöppel
authors.affiliation: Institute of Pathology, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Esposito
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D010641:Phenotype; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D051901:Smad4 Protein / Q000235:genetics; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; C497796:SMAD4 protein, human; D051901:Smad4 Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras)