title: Cyclin D1, p16(INK) (4A) and p27(Kip1) in pancreatic adenocarcinoma: assessing prognostic implications through quantitative image analysis.
abstract: The prognostic significance of cyclin D1, p16(INK) (4A) and p27(Kip1) expression has been documented in several human malignancies; however, their prognostic potential in pancreatic adenocarcinoma is still unclear. This study aimed to assess the correlation of the aforementioned molecules with clinicopathological parameters and prognosis. Sixty patients with pancreatic ductal adenocarcinoma underwent surgical resection at a single institution; immunohistochemical staining of the studied markers was quantified by Ιmage analysis system. Cyclin D1 overexpression was positively associated with grade, neural infiltration and vascular invasion, whereas p27 positively correlated with age. Higher cyclin D1 expression indicated poorer survival (adjusted HR = 9.75, 95%CI: 1.48-64.31, p = 0.018, increment: one unit in H-score), whereas a marginal trend toward an association between p16 positivity and improved survival was observed (adjusted HR = 0.58, 95%CI: 0.32-1.05, p = 0.072 regarding positive vs negative cases). No significant association with overall survival was noted regarding p27. In conclusion, cyclin D1 overexpression and possibly p16 loss of expression in pancreatic adenocarcinoma seem to be adverse prognostic factors, whereas p27 expression did not seem to possess such prognostic properties. Further validation of the present findings in studies encompassing larger samples seems to be needed.
authors: 3rd Surgical Clinic of George Gennimatas General Hospital, Mesogeion Ave 154, Athens, 156 69, Greece.
authors: Despoina
authors: D
authors: Georgiadou
authors: Theodoros N
authors: TN
authors: Sergentanis
authors: Stratigoula
authors: S
authors: Sakellariou
authors: George M
authors: GM
authors: Filippakis
authors: Flora
authors: F
authors: Zagouri
authors: Dimitris
authors: D
authors: Vlachodimitropoulos
authors: Theodora
authors: T
authors: Psaltopoulou
authors: Andreas C
authors: AC
authors: Lazaris
authors: Efstratios
authors: E
authors: Patsouris
authors: George C
authors: GC
authors: Zografos
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics*; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27
keywords: Cyclin D1; image analysis; p16; p27; pancreatic adenocarcinoma