Traditional and emerging molecular markers in neuroblastoma prognosis: The good, the bad and the ugly

Abstract.

Background: Neuroblastomas (NB) are a heterogeneous group of childhood tumours with a wide range of likelihood for tumour progression. As traditional parameters do not ensure completely accurate prognostic grouping, new molecular markers are needed for assessing the individual patient's prognosis more precisely. Patients and Methods: 133 NB of all stages were analysed in blind-trial fashion for telomerase activity (TA), expression of survivin, and MYCN status. These data were correlated with other traditional prognostic indicators and disease outcome. Results and Conclusions: TA is a powerful independent prognostic marker for all stages and is capable of differentiating between good and poor outcome in putative “favourable” clinical or biological subgroups of NB patients. High survivin expression is associated with an adverse outcome, but is more difficult to interprete than TA because survivin expression needs to be accurately quantified to be of predictive value. We propose an extended progression model for NB including emerging prognostic markers, with emphasis on telomerase activity.

Hintergrund: Neuroblastome (NB) sind eine heterogene Gruppe kindlicher Tumoren mit einer großen Variabilität der Wahrscheinlichkeit der Tumorprogression. Da traditionelle Parameter keine vollständig genauen prognostischen Vorhersagen erlauben, sind neue molekulare Marker zur Prognoseeinschätzung erforderlich. Patienten und Methoden: 133 NB aller Stadien wurden im Blindversuch auf Telomeraseaktivität (TA), Survivin-Expression und den N-MYC-Status untersucht. Diese Daten wurden mit anderen traditionellen prognostischen Parametern und dem Krankheitsverlauf korreliert. Ergebnisse und Schlussfolgerung: Telomeraseaktivität ist ein sehr aussagekräftiger, unabhängiger prognostischer Marker für alle Stadien und vermag auch in den vermeintlich günstigen klinischen oder biologischen Untergruppen der NB zwischen einem günstigen bzw. ungünstigen Krankheitsverlauf zu unterscheiden. Eine hohe Survivin-Expression ist auch mit einem ungünstigen Krankheitsverlauf korreliert, ist aber schwieriger zu interpretieren als TA, da ein prädiktiver Wert nur durch genaue Quantifizierung erreicht wird. Wir propagieren eine erweitertes Progressionsmodell des Neuroblastoms unter Einbeziehung neuer prognostischer Marker mit Betonung der Telomeraseaktivität.

Key words

Neuroblastoma - telomerase - survivin - progression model

Schlüsselwörter

Neuroblastom - Telomerase - Survivin - Progressionsmodell

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