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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.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Mora J,Gerald WL,Cheung NK

doi

10.1016/s0304-3835(03)00094-6

keywords:

subject

Has Abstract

pub_date

2003-07-18 00:00:00

pages

119-24

issue

1-2

eissn

0304-3835

issn

1872-7980

pii

S0304383503000946

journal_volume

197

pub_type

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