MB-108: EXPRESSION OF TROPOMYOSIN RECEPTOR KINASE C (TrkC) HAS NO MAJOR IMPACT ON THE RESPONSE TO THERAPY OF MEDULLOBLASTOMA IN VITRO AND IN A CLINICAL PATIENT COHORT

BACKGROUND: High mRNA expression of the tropomyosin receptor kinase C (TrkC) has been associated with favorable survival in medulloblastoma patients. A not yet tested explanation could be that TrkC mRNA expression modulates the response to therapy. PATIENTS AND METHODS: Medulloblastoma-derived cell line DAOY, stably transfected to overexpress TrkC (clone DAOY-TrkC) and compared to a control (clone DAOY-EV, empty vector transfected), was grown under serum-free conditions (± TrkC ligand neutrophin-3, NT-3) and cell viability was tested after irradiation or incubation with chemotherapeutic drugs after 72 h using the MTS-assay. Neuroradiologic response to postoperative chemotherapy or craniospinal irradiation (CSI) of medulloblastoma patients aged 3-21 years with postoperative residual disease treated within the consecutive trials HIT'91/HIT2000 was compared to TrkC mRNA expression in their tumor samples. RESULTS: Cell viability of DAOY-TrkC compared to DAOY-EV was not different after incubation with increasing doses of cisplatin (0-4.8 µg/ml), etoposide (0-1.3 µg/ml), or vincristine (0-20 ng/ml), and irradiation (2, 5, 10 Gy). While TrkC mRNA expression tended to be higher in non-responders (n = 5/19) to postoperative CSI (p = 0.03, ratio 15.5, 95% CI 9-267), this was the case in responders (n = 23/43) to chemotherapy (p = 0.04, ratio 6.1, 95% CI 1.1-35, both analyzed with Mann-Withney U test and not significant after Bonferroni adjustment). CONCLUSIONS: TrkC mRNA expression was not associated with a considerable improvement in response to therapy neither in vitro nor in a MB patient cohort. The study is limited by a relatively small medulloblastoma patient cohort and the availability of only one TrkC mRNA overexpressing medulloblastoma cell line.