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Original Article |
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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