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10.1245/s10434-007-9469-6
Annals of Surgical Oncology 14:2591-2599 (2007)
© 2007 Society of Surgical Oncology
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Original Article

Prognostic Implications of Netrin-1 Expression and Its Receptors in Patients with Adenocarcinoma of the Pancreas

Björn-Christian Link, MD1, Uta Reichelt, MD2, Matthias Schreiber, MS1, Jussuf T. Kaifi, MD1, Robin Wachowiak, MD1, Dean Bogoevski, MD1, Michael Bubenheim, PhD3, Guel Cataldegirmen, MD1, Karim A. Gawad, MD1, Rana Issa, MD2, Susann Koops, MD2, Jakob R. Izbicki, MD, FACS1 and Emre F. Yekebas, MD1

1 Department of General, Visceral and Thoracic Surgery, University Medical Center of Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
2 Department of Pathology, University Medical Center of Hamburg-Eppendorf, Hamburg, Germany
3 Department of Medical Biometry and Epidemiology, University Medical Center of Hamburg-Eppendorf, Hamburg, Germany

Correspondence: Address correspondence and reprint requests to: Björn-Christian Link, MD; E-mail: . blink{at}uke.uni-hamburg.de

Background: To assess the interaction between the expression of netrin-1 or of its receptors to the prognosis of ductal adenocarcinoma of the pancreas.

Methods: In 82 patients with resectable pancreatic adenocarcinoma who underwent curative operation, the expression patterns of netrin-1, deleted in colorectal carcinomas (DCC), UNC5H3, and neogenin were determined by immunohistochemical staining. Kaplan-Meier analysis was performed to assess the prognostic relevance of the examined expression patterns.

Results: Median follow-up was 15 ± 19.9 months (range, 4–108 months). Patients suffering from tumors with no or little expression of netrin-1 (n = 67) had a median recurrence-free survival of 10 months (95% CI, 7–13 months), while a middle to strong expression (n = 15) was associated with a significantly worse median recurrence-free survival of only four months (95% CI, three to five months, p = 0.0165). Overall and recurrence-free survival showed no significant differences between the different expression patterns of DCC, UNC5H3 or neogenin. Netrin-1 expression had significant impact (p = 0.001) on overall survival of patients suffering from poorly differentiated tumors. Stratification according to the nodal status revealed significant influence (p = 0.007) of UNC5H3 expression on the overall survival of patients with pN1 status.

Conclusion: Expression of netrin-1 has significant impact on time to tumor relapse in adenocarcinoma of the pancreas. Netrin-1 expression is associated with worse outcome in poorly differentiated pancreatic adenocarcinomas. Risk-stratification according to the UNC5H3 receptor expression pattern shows that node positive patients (pN1) with no to little UNC5H3 expression carry a significantly worse prognosis than those with middle to strong UNC5H3 expression.

Key Words: Pancreatic cancer • Immunohistochemistry • Netrin-1 • UNC5H • DCC • Neogenin






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