Neuroblastoma: Impact of Biological Characteristics on Treatment Strategies

Abstract

Neuroblastoma (NB) is the most frequent solid tumour in early childhood. NBs are extremely heterogeneous in terms of their biological characteristics and the clinical behaviour which ranges from lethal disease to spontaneous regression and/or differentiation. Genetically, the heterogeneity of these tumours is reflected mainly by differences in the DNA content, presence of chromosome lp deletions and amplification of the proto-oncogene N-myc. Up to now, only the prognostic impact of N-myc amplification, based on a large series of analysed tumour samples, was established and is now used as the discriminating factor for treatment stratification in a newly developed European protocol. The influence of other genetic aberrations, i.e. dellp36, t(l;17), ploidy and expression of certain proteins, such as nerve growth factor (NGF) receptor proteins and CD44, on the biological behaviour were studied only in a limited number of cases. We will review the literature and outline our own observations dealing with the peculiar phenomena observed in some NBs, i. e. spontaneous regression and/or maturation.

Neuroblastoma screening in infants postponed after the sixth month of age: A trial to reduce “overdiagnosis” and to detect cases with “unfavorable” biologic features

“…The 1p deletion is the most frequent structural alteration in stage 4 tumors [53] and also in localized or stage 4s tumors which progressed later on into stage 4 tumors [46]. Interestingly, this aberration has never been observed in tumors undergoing spontaneous regression or maturation [46,[57][58][59]. However, the predictive relevance of the 1p deletion as an independent prognostic marker has still to be clarified [49,50,53].…”

Clinical Application of Molecular Cytogenetics in Solid Tumors

“…Cytogenetic findings in neuroblastoma, a tumor of early childhood arising from adrenal medulla or sympathetic nervous system, were recognized as independent prognostic factors [review in 61]. The clinical course of neuroblastoma ranges from spontaneous regression to very aggressive behavior.…”

“…Intact chromosome 1 and triploidy of neuroblastoma cells (evaluable by FISH and DNA flow cytometry, respectively) indicate spontaneous organoid maturation, whereas deletion at 1p36, N-myc amplification, and di-and tetraploidy represent unfavorable features [61][62][63][64]. The feasibility of FISH to determine the prognostically relevant chromosomal changes (chromosome 1 ploidy status, 1p deletion, N-myc amplification) as part of diagnostic procedures was demonstrated [61,63,65]. Detection of N-myc amplification located on chromosome 2p23 by FISH was shown to be superior to labor-intensive Southern blot analysis, since tumor cells can be selectively evaluated and intratumor heterogeneity is recorded.…”