VEGF and Id-1 in pancreatic adenocarcinoma: prognostic significance and impact on angiogenesis.
OBJECTIVE
The significance of vascular endothelial growth factor (VEGF) and inhibitor of differentiation/DNA synthesis (Id-1) in tumor neoangiogenesis and tumor progression in pancreatic ductal adenocarcinoma (PDAC) is still unclear. Given the central role of VEGF in cancer angiogenesis and the inconclusive results on Id-1 expression in PDAC, it is of great interest to investigate whether Id-1 and VEGF expression are associated with angiogenesis and prognosis in PDAC.


METHODS
Paraffin-embedded specimens from 60 consecutive patients with PDAC were immunostained for VEGF, Id-1 and CD34 and staining quantification was assessed by Image analysis system. The correlations among the expression of individual angiogenic factors and microvessel density (MVD), clinicopathologic features and clinical prognosis were analyzed.


RESULTS
Id-1 and VEGF Positive Activity Indices (PAIs) closely correlated with each other. MVD positively correlated with both Id-1 and VEGF expression. More advanced T and N status correlated with more intense expression of Id-1, VEGF and higher MVD. With regard to prognostic significance higher Id-1 PAI (adjusted HR = 1.69, 95%CI: 1.10-2.59, p = 0.017), higher VEGF PAI (adjusted HR = 2.66, 95%CI: 1.09-6.50, p = 0.032), and MVD (adjusted HR = 1.55, 95%CI: 1.27-1.88, p < 0.001) were associated with poorer survival.


CONCLUSIONS
VEGF and Id-1 overexpression were found to be associated with high MVD and emerged as adverse prognostic factors in terms of patient survival in PDAC. The potential of selective anti-angiogenic targeting therapy for pancreatic malignancies should prompt further validation of the present findings in studies encompassing larger samples and more elaborate techniques.
3rd Surgical Clinic of George Gennimatas General Hospital, Mesogeion Ave 154, 156 69 Athens, Greece. Electronic address: desangeor@yahoo.gr.
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Georgiadou
Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, M. Asias 75, Goudi, 11527 Athens, Greece. Electronic address: tsergentanis@yahoo.gr.
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Sergentanis
1st Department of Pathology, National and Kapodistrian University of Athens, Mikras Asias 75, 11527 Athens, Greece. Electronic address: 7791j@otenet.gr.
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Sakellariou
1st Department of Propaedeutic Surgery, Hippokratio Hospital, Vassilissis Sophias Avenue 114, 115 27 Athens, Greece. Electronic address: gfilipp@hotmail.com.
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Filippakis
1st Department of Propaedeutic Surgery, Hippokratio Hospital, Vassilissis Sophias Avenue 114, 115 27 Athens, Greece. Electronic address: florazagouri@yahoo.co.uk.
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Zagouri
Department of Forensic Pathology and Toxicology, Medical School, University of Athens, Mikras Asias 75, 11527 Athens, Greece. Electronic address: dvlacho@med.uoa.gr.
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Vlachodimitropoulos
Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, M. Asias 75, Goudi, 11527 Athens, Greece. Electronic address: tpsaltop@med.uoa.gr.
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Psaltopoulou
1st Department of Pathology, National and Kapodistrian University of Athens, Mikras Asias 75, 11527 Athens, Greece. Electronic address: alazaris@med.uoa.gr.
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Lazaris
1st Department of Pathology, National and Kapodistrian University of Athens, Mikras Asias 75, 11527 Athens, Greece. Electronic address: efpatsouris@med.uoa.gr.
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Patsouris
1st Department of Propaedeutic Surgery, Hippokratio Hospital, Vassilissis Sophias Avenue 114, 115 27 Athens, Greece. Electronic address: gzografo@med.uoa.gr.
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Zografos
D000230:Adenocarcinoma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism*; D008297:Male; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D018952:Antigens, CD34; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
Id-1; Image analysis; MVD; Pancreatic adenocarcinoma; VEGF