title: Telomerase activity as a prognostic factor in neuroblastomas.
abstract: Neuroblastoma is the most common extracranial solid tumor of early childhood. This tumor demonstrates significant heterogeneity with respect to pathologic, genetic, and clinical features. The outcome varies from spontaneous regression or maturation to rapid progression, despite aggressive therapy. Prognostic factors have been found that identify those tumors which have a high probability of aggressive behavior; these factors include unfavorable histology, MYCN copy number, deletions of the short arm of chromosome 1, DNA content, and TRK-A (high-affinity receptor protein for nerve growth factor) expression. Recent studies have suggested that high levels of telomerase activity also correlate with poor clinical outcome. We investigated this relationship in 40 patients with untreated neuroblastoma, using a PCR-ELISA assay for telomerase activity. In these patients, 23 tumors had no or minimal telomerase activity whereas 15 had high levels of activity. In two tumors, telomerase activity was not assessable. There was significant correlation between the telomerase activity and MYCN copy number, 1p deletions, and TRK-A expression, as well as patient age, clinical stage, and outcome. The histological classification of the tumors was not significantly different between the two groups, being predominantly unfavorable by the Shimada classification. In addition, for 17 patients tumor tissue was assessed for telomerase activity post-chemotherapy. In those cases where the tumor was negative for telomerase activity before and after chemotherapy, the patients uniformly did well. In cases where the tumor was positive before and negative or weakly positive after treatment, two of the seven patients did well clinically. However, in cases that were positive after chemotherapy, all had recurrence or died. In conclusion, telomerase activity appears to be a prognostic factor for neuroblastomas. In addition, assessment of tumors post-chemotherapy may be a further indicator of clinical outcome.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada.
authors.forename: C J
authors.initials: CJ
authors.lastname: Streutker
authors.forename: P
authors.initials: P
authors.lastname: Thorner
authors.forename: N
authors.initials: N
authors.lastname: Fabricius
authors.forename: S
authors.initials: S
authors.lastname: Weitzman
authors.forename: M
authors.initials: M
authors.lastname: Zielenska
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1; D004273:DNA, Neoplasm / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D018628:Gene Dosage; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000175:diagnosis* / Q000201:enzymology* / Q000235:genetics / Q000556:secondary / Q000628:therapy; D016133:Polymerase Chain Reaction; D011379:Prognosis; D020917:Receptor, trkA / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D004273:DNA, Neoplasm; D020917:Receptor, trkA; D019098:Telomerase