BACKGROUND: Netrin-1 and its receptors, DCC, UNC5H and Neogenin have been shown to play a major role during nervous system development. However, they have also been described recently as putative tumor suppressors and survival factors in various tumor entities. This study was performed to assess if expression of Netrin-1 and its receptors in pancreatic adenocarcinoma is correlated to survival or time to tumor recurrence. METHODS: Patients with resectable pancreatic adenocarcinoma, who had undergone radical operation (pancreaticoduodenectomy) between April 1992 and November 2002 in the Department of General, Visceral and Thoracic Surgery of the University Medical Center of Hamburg-Eppendorf, Germany, were included. Patients receiving adjuvant chemoradiation or chemotherapy, as well as patients with R2-resection or patients who died within 90 days after surgery were excluded. Informed consent was obtained from all the patients before their inclusion in the study. Paraffin-embedded sections of the primary tumor were examined regarding their expression patterns of Netrin-1, DCC, UNC5H3 and Neogenin using immunohistochemical staining. Kaplan-Meier analyses were performed to assess the prognostic relevance of the examined expression patterns. RESULTS: A total of 82 patients met the study’s criteria. Median age was 62±10.9 years (range, 33-83). Median follow-up was 15±19.9 months (range, 4-108). 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), while a middle or strong expression (n=15) was associated with a significantly lower median recurrence-free survival of only 4 months (95%CI, 3-5) (p=0.0165). Median overall survival in the two groups was 16 months (95%CI, 13-19) and 9 months (95%, 3-15), respectively (p=0.314). Overall and recurrence-free survival showed no significant differences between the different expression patterns of DCC, UNC5H3 or Neogenin. CONCLUSIONS: Expression of Netrin-1 has significant impact on time to tumor relapse in adenocarcinoma of the pancreas. Three of its six known receptors, namely DCC, UNC5H3 and Neogenin, have no influence on survival. To elucidate the underlying pathophysiology and the role of the additional receptors in this context further studies have to be performed.