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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Priv.-Doz. Dr. med. Christopher Poremba
Gerhard-Domagk-Institute of Pathology Westfälische
Wilhelms-University
Domagkstraße 17
48149 Münster
Germany
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0 11-49-2 51-8 35 54 49
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