title: Altered interphase fluorescence in situ hybridization profiles of chromosomes 4, 8q24, and 9q34 in pancreatic ductal adenocarcinoma are associated with a poorer patient outcome.
abstract: Most patients with pancreatic ductal adenocarcinoma (PDAC) die within 6 months of diagnosis. However, 20% to 25% patients undergoing total tumor resection remain alive and disease-free 5 years after diagnostic surgery. Few studies on tumor markers have predicted patient prognosis and/or survival. We evaluated the effect of tumor cytogenetic copy number changes detected by interphase fluorescence in situ hybridization on overall survival (OS) of 55 PDAC patients. The prognostic value of copy number changes showing an effect on OS was validated in an external cohort of 44 surgically resected PDAC patients by comparative genomic hybridization arrays, and the genes coded in altered chromosomes with prognostic value were identified by high-density single-nucleotide polymorphism arrays in 20 cases. Copy number changes of chromosomes 4 and 9q34 with gains of 8q24 were independently associated with shorter OS. On the basis of these three chromosomal alterations, a score is proposed that identifies patients with significantly different (P < 0.001) 5-year OS rates: 60% ± 20%, 16% ± 8%, and 0% ± 0%, respectively. Our results show an association between tumor cytogenetics and OS of PDAC patients and provide the basis for further prognostic stratification of patients undergoing complete tumor resection. Further studies to identify specific genes coded in these chromosomes and their functional consequences are necessary to understand the clinical effect of these changes.
authors.affiliation: Cytometry General Service-NUCLEUS, Department of Medicine and Cancer Center Research and Institute of Molecular Biology and Cellular Oncology, Institute of Biomedical Research of Salamanca, University of Salamanca, Salamanca, Spain.
authors.forename: María L
authors.initials: ML
authors.lastname: Gutiérrez
authors.affiliation: Department of General and Digestive Surgery, University Hospital of Salamanca, Salamanca, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Muñoz-Bellvis
authors.affiliation: Hematology Service, Institute of Biomedical Research of Salamanca, University Hospital of Salamanca, Cancer Center Research and Institute of Molecular Biology and Cellular Oncology, Salamanca, Spain.
authors.forename: María E
authors.initials: ME
authors.lastname: Sarasquete
authors.affiliation: Cytometry General Service-NUCLEUS, Department of Medicine and Cancer Center Research and Institute of Molecular Biology and Cellular Oncology, Institute of Biomedical Research of Salamanca, University of Salamanca, Salamanca, Spain.
authors.forename: David G
authors.initials: DG
authors.lastname: Hernández-Mejía
authors.affiliation: Department of Pathology, University Hospital of Salamanca, Salamanca, Spain.
authors.forename: María del Mar
authors.initials: Mdel M
authors.lastname: Abad
authors.affiliation: Department of Pathology, University Hospital of Salamanca, Salamanca, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Bengoechea
authors.affiliation: Hematology Service, Institute of Biomedical Research of Salamanca, University Hospital of Salamanca, Cancer Center Research and Institute of Molecular Biology and Cellular Oncology, Salamanca, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Corchete
authors.affiliation: Cytometry General Service-NUCLEUS, Department of Medicine and Cancer Center Research and Institute of Molecular Biology and Cellular Oncology, Institute of Biomedical Research of Salamanca, University of Salamanca, Salamanca, Spain.
authors.forename: María
authors.initials: M
authors.lastname: González-González
authors.affiliation: Department of General and Digestive Surgery, University Hospital of Salamanca, Salamanca, Spain.
authors.forename: Jacinto
authors.initials: J
authors.lastname: García-García
authors.affiliation: Hematology Service, Institute of Biomedical Research of Salamanca, University Hospital of Salamanca, Cancer Center Research and Institute of Molecular Biology and Cellular Oncology, Salamanca, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Gonzalez
authors.affiliation: Cytometry General Service-NUCLEUS, Department of Medicine and Cancer Center Research and Institute of Molecular Biology and Cellular Oncology, Institute of Biomedical Research of Salamanca, University of Salamanca, Salamanca, Spain.
authors.forename: Ines
authors.initials: I
authors.lastname: Mota
authors.affiliation: Cytometry General Service-NUCLEUS, Department of Medicine and Cancer Center Research and Institute of Molecular Biology and Cellular Oncology, Institute of Biomedical Research of Salamanca, University of Salamanca, Salamanca, Spain. Electronic address: orfao@usal.es.
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.affiliation: Cytometry General Service-NUCLEUS, Department of Medicine and Cancer Center Research and Institute of Molecular Biology and Cellular Oncology, Institute of Biomedical Research of Salamanca, University of Salamanca, Salamanca, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Sayagues
mesh_terms: D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000503:physiopathology; D002877:Chromosomes, Human; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000503:physiopathology; D016896:Treatment Outcome