Prognostic implications of netrin-1 expression and its receptors in patients with adenocarcinoma of the pancreas.
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.


CONCLUSIONS
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.
Link
Björn-Christian
BC
Department of General, Visceral and Thoracic Surgery, University Medical Center of Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. blink@uke.uni-hamburg.de
Reichelt
Uta
U
Schreiber
Matthias
M
Kaifi
Jussuf T
JT
Wachowiak
Robin
R
Bogoevski
Dean
D
Bubenheim
Michael
M
Cataldegirmen
Guel
G
Gawad
Karim A
KA
Issa
Rana
R
Koops
Susann
S
Izbicki
Jakob R
JR
Yekebas
Emre F
EF
D000230:Adenocarcinoma / Q000378:metabolism* / Q000601:surgery; D014408:Biomarkers, Tumor / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008197:Lymph Node Excision; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009414:Nerve Growth Factors / Q000378:metabolism*; D000075386:Netrin Receptors; D000075388:Netrin-1; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000601:surgery; D016577:Pancreaticoduodenectomy; D011379:Prognosis; D016016:Proportional Hazards Models; D011956:Receptors, Cell Surface / Q000378:metabolism; D018709:Statistics, Nonparametric; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D014408:Biomarkers, Tumor; D008565:Membrane Proteins; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C091279:neogenin; D000075388:Netrin-1; D017871:Calcium-Calmodulin-Dependent Protein Kinases