Evolving significance of prognostic markers associated with new treatment strategies in neuroblastoma Journal Article


Authors: Mora, J.; Gerald, W. L.; Cheung, N. K. V.
Article Title: Evolving significance of prognostic markers associated with new treatment strategies in neuroblastoma
Abstract: The striking differences in the natural history of clinical subgroups of neuroblastoma (NB), and the evolving therapeutic approaches for each, makes it imperative for prognostic markers to be reevaluated within individual clinical categories. At least one third of NB cases present without distant metastasis and cytotoxic therapy does not alter the natural history. We carried out a retrospective analysis of archived tumor samples. Fifty-seven of these patients had local-regional (LR) NB and were managed conservatively, initially treated with surgery alone. Among the biologic and clinical features analyzed including age, stage, histology, ploidy, MYCN, and 1p36, 1p22, 11q, 14q, 9p and 19q loss of heterozygosity (LOH) in multivariate analysis, diploidy was one of the most significant factors associated with progression-free survival and stage 4 progression. Clonal ploidy heterogeneity was common in LR NB. A predominant near-triploid clonal population was found in most cases of non-progressing LR NB tumors whereas progressing LR NB cases had a predominant diploid clone. We also reviewed the prognostic factors among 84 stage 4 NB cases treated with the N5, N6 or N7 protocols at MSKCC from 1987 to 1999. Traditional markers such as lactate dehydrogenase (LDH), ferritin, age and MYCN status were not prognostic in the univariate analysis. 11q23 and 1p22 LOH were correlated with better survival. These results highlight the evolving significance of prognostic analysis in homogeneous clinical groups undergoing similar treatments. To further characterize the gene expression profile between local-regional and metastatic NB, we carried out Microarray analysis of 41 NB tumors and 12 NB cell lines, using the Affymetrix Genechip Human Genome U95 Set™. Distinct gene expression patterns between metastatic and non-metastatic NB tumors have been identified. Validation of these results and further mechanistic studies may shed new light on the biology of metastasis in human NB. © 2003 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: cancer survival; treatment outcome; histopathology; cancer growth; cancer risk; validation process; conference paper; cancer staging; neoplasm staging; metastasis; neoplasm recurrence, local; gene expression; gene expression profiling; tumor markers, biological; chromosome 9p; risk factors; relapse; tumor marker; risk factor; risk assessment; risk; correlation analysis; neuroblastoma; microarray analysis; disease progression; lactate dehydrogenase; multivariate analysis; dna microarray; age distribution; heterozygosity loss; loss of heterozygosity; oncogene c myb; clinical trials; chromosome 11q; ferritin; genetic heterogeneity; chromosome 14q; chromosome 1p; chromosome 19q; mycn; 19q13; prognostic markers; ploidy; triploidy; ploidies; humans; prognosis; human; priority journal; genetic classification; local-regional neuroblastoma
Journal Title: Cancer Letters
Volume: 197
Issue: 1-2
ISSN: 0304-3835
Publisher: Elsevier Ireland Ltd.  
Date Published: 2003-07-18
Start Page: 119
End Page: 124
Language: English
DOI: 10.1016/s0304-3835(03)00094-6
PUBMED: 12880970
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 25 September 2014 -- Source: Scopus
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MSK Authors
  1. Nai-Kong Cheung
    650 Cheung
  2. William L Gerald
    375 Gerald