title: Loss of the CBX7 protein expression correlates with a more aggressive phenotype in pancreatic cancer.
abstract: Polycomb group (PcG) proteins function as multiprotein complexes and are part of a gene regulatory mechanism that determines cell fate during normal and pathogenic development. Several studies have implicated the deregulation of different PcG proteins in neoplastic progression. Pancreatic ductal adenocarcinoma is an aggressive neoplasm that follows a multistep model of progression through precursor lesions called pancreatic intraepithelial neoplasia (PanIN). Aim of this study was to investigate the role of PcG protein CBX7 in pancreatic carcinogenesis and to evaluate its possible diagnostic and prognostic significance. We analysed by immunohistochemistry the expression of CBX7 in 210 ductal pancreatic adenocarcinomas from resection specimens, combined on a tissue microarray (TMA) including additional 40 PanIN cases and 40 normal controls. The results were evaluated by using receiver operating characteristic (ROC) curve analysis for the selection of cut-off scores and correlated to the clinicopathological parameters of the tumours and the outcome of the patients. Expression of E-cadherin, a protein positively regulated by CBX7, was also assessed. A significantly differential, and progressively decreasing CBX7 protein expression was found between normal pancreatic tissue, PanINs and invasive ductal adenocarcinoma. Loss of CBX7 expression was associated with increasing malignancy grade in pancreatic adenocarcinoma, whereas the maintenance of CBX7 expression showed a trend toward a longer survival. Moreover, loss of E-cadherin expression was associated with loss of CBX7 and with a trend towards worse patient survival. These results suggest that CBX7 plays a role in pancreatic carcinogenesis and that its loss of expression correlates to a more aggressive phenotype.
authors.affiliation: Second Department of Pathology, University of Athens, Attikon University Hospital, Haidari, Athens, Greece.
authors.forename: Eva
authors.initials: E
authors.lastname: Karamitopoulou
authors.forename: Pierlorenzo
authors.initials: P
authors.lastname: Pallante
authors.forename: Inti
authors.initials: I
authors.lastname: Zlobec
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
authors.forename: Vincenza
authors.initials: V
authors.lastname: Carafa
authors.forename: Thomas
authors.initials: T
authors.lastname: Schaffner
authors.forename: Markus
authors.initials: M
authors.lastname: Borner
authors.forename: Ioannis
authors.initials: I
authors.lastname: Diamantis
authors.forename: Francesco
authors.initials: F
authors.lastname: Esposito
authors.forename: Thomas
authors.initials: T
authors.lastname: Brunner
authors.forename: Arthur
authors.initials: A
authors.lastname: Zimmermann
authors.forename: Antonella
authors.initials: A
authors.lastname: Federico
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D063150:Polycomb Repressive Complex 1; D011379:Prognosis; D040081:Protein Array Analysis / Q000379:methods; D012372:ROC Curve; D012097:Repressor Proteins / Q000378:metabolism*; D055815:Young Adult
chemical_list: C503627:CBX7 protein, human; D015820:Cadherins; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1