Telomerase activity distinguishes between neuroblastomas with good and poor prognosis.
BACKGROUND
Treatment of neuroblastoma has remained a major challenge in pediatric oncology because the assessment of the individual prognosis, particularly in disseminated disease is still obscure. Previous studies have correlated clinical outcome with activity levels of telomerase, a cellular reverse transcriptase which has been detected in the majority of human malignant tumors.


METHODS
In this blind-trial study, a non-radioactive telomeric repeat amplification protocol (TRAP) with an internal telomerase-assay standard was used on an automated laser fluorescence sequencer for the detection and semiquantitative analysis of telomerase activity (TA) in 67 neuroblastomas of all clinical stages from the German Neuroblastoma Trial and 2 ganglioneuromas. TA levels were correlated with event-free and overall survival 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 regard to all tumor stages. Multivariate analysis revealed TA as an independent prognostic marker. In particular, the analysis of TA in IVS neuroblastomas distinguished two different prognostic groups.


CONCLUSIONS
Our data suggest that TA is an independent prognostic marker in neuroblastoma which, in combination with other markers such as MYCN, may proof useful in assessing the individual patient's prognosis.
Poremba
C
C
Gerhard-Domagk-Institute of Pathology, University of Münster, Germany.
Willenbring
H
H
Hero
B
B
Christiansen
H
H
Schäfer
K L
KL
Brinkschmidt
C
C
Jürgens
H
H
Böcker
W
W
Dockhorn-Dworniczak
B
B
D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D005260:Female; D005729:Ganglioneuroma / Q000145:classification / Q000201:enzymology* / Q000473:pathology; D005784:Gene Amplification; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009367:Neoplasm Staging / Q000379:methods; D009447:Neuroblastoma / Q000145:classification / Q000201:enzymology* / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis; D019098:Telomerase / Q000378:metabolism*
D019098:Telomerase