Neurotrophin receptor TrkC predicts good clinical outcome in medulloblastoma and other primitive neuroectodermal brain tumors

Background: Neurotrophins and their cognate receptors TrkA, TrkB and TrkC r egulate proliferation, differentiation and death of neuronal progenitor cel ls and may be implicated in the progression of medulloblastoma and other pr imitive neuroectodermal brain tumors (PNET). These common childhood brain t umors are composed of morphologically undifferentiated cells that have impo rtant similarities to neuroectodermal progenitor cells of the developing CN S. Patients and Methods: To identify biologic prognostic factors in childho od PNET we determined expression levels of TrkC mRNA in tumor samples from 87 PNET patients by in situ hybridization. Comparison of TrkC mRNA expressi on levels with clinical variables was performed using univariate and multiv ariable Cox regression analysis. Results: Cox regression analysis revealed that children with tumors expressing no or little TrkC mRNA had a 4.8-fold (p < 0.00005) greater risk of death than children with tumors with high Trk C mRNA expression. This hazard ratio remained consistent after adjusting fo r clinical variables. Five-year survival was 89% for patients with PNETs ex pressing high levels of TrkC mRNA and 47% for patients with PNETs expressin g little or no levels of TrkC mRNA (log rank; p < 0.00005). Conclusions: Th e TrkC neurotrophin receptor appears to be a powerful independent prognosti c factor in PNET and may have a role in patient assignment to risk-based tr eatment strategies.