TrkC expression predicts good clinical outcome in primitive neuroectodermal brain tumors

Purpose: To identify biologic prognostic factors in childhood primitive neu roectodermal tumors (PNET), including medulloblastoma, that accurately defi ne patient groups with sufficiently good prognosis to permit a reduction in treatment intensity. Patients and Methods: We determined expression levels of the neurotrophin r eceptor TrkC mRNA in formalin-fixed tumor samples from 87 well characterize d PNET patients using in situ hybridization. Comparison of TrkC mRNA expres sion levels with clinical and other laboratory variables was performed usin g univariate and multivariate Cox regression analysis. Results: High TrkC mRNA expression wets found to be associated more with hi gher 5-year cumulative survival rate than was low TrkC mRNA expression (89% v 46%, respectively). When compared with established clinical prognostic f actors and laboratory variables of potential prognostic significance, TrkC mRNA expression, by univariate analysis, was found to be the single most po werful predictor of outcome (hazards ratio, 4.81; P < .00005), exceeding al l clinical prognostic factors. In multivariate analysis, the hazards ratio remained significant (P < .00005). Conclusion: High TrkC mRNA expression in PNET is a powerful independent pre dictor of favorable clinical outcome. Assessment of TrkC mRNA levels may ai d in treatment planning for patients with PNETs and should be incorporated prospectively into PNET clinical trials. J Clin Oncol 18:1027-1035. (C) 200 0 by American Society of Clinical Oncology.