uPAR und c-MYC beim duktalen Adenokarzinom des Pankreas

Imaging of uPAR and c-MYC in pancreatic cancer using FISH

by Frieder Fuchs
Doctoral thesis
Date of Examination:2018-08-22
Date of issue:2018-08-16
Advisor:Dr. Julia Kitz
Referee:Prof. Dr. Philipp Ströbel
Referee:Prof. Dr. Peter Burfeind
Referee:Prof. Dr. Margarete Schön
Persistent Address: http://dx.doi.org/10.53846/goediss-7018

 

 

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Abstract

English

The dismal prognosis of pancreatic cancer is closely related to aggressive tumor development that leads to diagnosis in advanced stages and limited curative concepts. Urokinase-type plasminogen activator receptor (uPAR) and c-myc are both well known cancer genes and have been repeatedly associated with particularly unfavorable prognosis in various types of cancer. The present study aimed to establish uPAR and c-myc amplification status as relevant risk markers in patients with pancreatic ductal adenocarcinoma (PDAC). We studied a collective of 60 clinically well characterized pancreatic cancer cases from a single institution for amplification of uPAR and c-myc using fluorescence in situ hybridiziation (FISH). To minimize potential confounders, all patients were in stage pT3 N1 and tumor grades 2/3. uPAR amplificiation was identified in 29 of 60 PDAC. 16 cases were low level (LL), 13 cases showed high level amplification (HL). The median survival of patients without amplification was 28,4 months compared to 15,5 months in LL cases and 12,4 months in HL cases (Cox-Mantel-test, p=0.027). Myc amplification was found in 32 cases. 12 cases were low level, 20 cases showed high level amplification. The median survival of patients without amplification was 27,5 months compared to 11,1 months in LL cases and 19,3 months in HL cases (Cox-Mantel-test, p=0.048). There was a statistical trend towards co-amplification of uPAR and myc (r=0.227, p=0.026). uPAR and myc amplification were not among the statistically significant parameters on multi-variate analysis (tumor stage, age at diagnosis). Both uPAR and myc amplification are indicators of a PDAC subgroup with particularly dismal prognosis and tend to occur in the same tumor. Further work will be needed to establish whether this observation represents only a coincidence or a synergy between two important oncogenes. uPAR is a promising target both for imaging purposes and targeted therapy and merits further investigation.
Keywords: uPAR
 
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