Telomerase activity distinguishes between neuroblastomas with good and poor prognosis

Background: Treatment of neuroblastoma has remained a major challenge in pe diatric oncology because the assessment of the individual prognosis, partic ularly in disseminated disease is still obscure. Previous studies have corr elated clinical outcome with activity levels of telomerase, a cellular reve rse transcriptase which has been detected in the majority of human malignan t tumors. Patients and methods: In this blind-trial study, a non-radioactive telomeri c repeat amplification protocol (TRAP) with an internal telomerase-assay st andard was used on an automated laser fluorescence sequencer for the detect ion and semiquantitative analysis of telomerase activity (TA) in 67 neurobl astomas of all clinical stages from the German Neuroblastoma Trial and 2 ga nglioneuromas. TA levels were correlated with event-free and overall surviv al rates and established prognostic markers such as MYCN. Results: TA was present in 14 of 69 (20%) samples, including 3 of 22 stage IVS, 8 of 14 stage IV, 1 of 10 stage III, 1 of 7 stage II and 1 of 14 stage I neuroblastomas and 0 of 2 ganglioneuromas. We found a strong statistical correlation between the presence of TA and poor clinical prognosis with re gard to all tumor stages. Multivariate analysis revealed TA as an independe nt prognostic marker. In particular, the analysis of TA in IVS neuroblastom as distinguished two different prognostic groups. Conclusions: Our data suggest that TA is an independent prognostic marker i n neuroblastoma which, in combination with other markers such as MYCN, may proof useful in assessing the individual patient's prognosis.