[Expression of the neurotrophin-receptor TrkB predicts outcome in nephroblastomas: results of a pilot-study].
BACKGROUND
The neurotrophin-receptor TrkB plays an important role in pathogenesis, biology and prognosis of neuroblastoma. Expression of TrkB on aggressive neuroblastomas leads to proliferation and survival of the tumor cells and is associated with an unfavorable prognosis. It is now known that Trk receptors are also expressed in extraneural tissues including the kidney.


METHODS
To study the role of the neurotrophin-receptor TrkB in nephroblastoma/Wilms' Tumor (WT), we determined TrkB mRNA expression by semiquantitative duplex RT-PCR in 39 primary WT. Comparison of mRNA expression levels with clinical variables was performed using Cox regression analysis.


RESULTS
The 5-year overall survival was significantly worse for patients with tumors expressing high levels of a functional TrkB-receptor (TrkBfull) in comparison to patients with low levels of TrkBfull (70 % versus 100 %, p=0.005). Conversely, children with tumors expressing high mRNA levels of a functionally inactive truncated TrkB receptor (TrkBtrunc) had a significantly higher 5-year overall survival rate in comparison to patients with low levels of TrkBtrunc (100 % versus 68 %, p=0.003). The hazard ratios for TrkBfull and TrkBtrunc remained significant after adjusting for tumor stage. All WT with high levels of TrkB also expressed the ligand brain-derived neurotrophic factor (BDNF).


CONCLUSIONS
Full-length and truncated TrkB appear to be important prognostic factors in WT. Their expression should be assessed prospectively in a larger panel of WT and may have a future role in patient assignment to risk-based treatment strategies. TrkB signaling may be reduced in WT with favorable outcome due to low numbers of TrkB receptors or a competitive effect of functionally inactive TrkBtrunc.
Eggert
A
A
Universitätskinderklinik Essen, Abteilung für Hämatologie/Onkologie, Germany. angelika.eggert@uni-essen.de
Grotzer
M A
MA
Zhao
H
H
Brodeur
G M
GM
Evans
A E
AE
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism*; D020812:Receptor, trkC / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012306:Risk; D016019:Survival Analysis; D009396:Wilms Tumor / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000628:therapy
D014408:Biomarkers, Tumor; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC
Die Expression des Neurotrophin-Rezeptors TrkB beeinflusst die Prognose von Nephroblastomen: Ergebnisse einer Pilotstudie.