Prognostic value of MDR1 gene expression in neuroblastoma: results of a multivariate analysis.
The prognostic value of the MDR1 gene expression in neuroblastoma (NB) was assessed in a multivariate analysis performed in a series of 84 patients (pts) taking into account the main known clinical and biological factors of the disease, i.e., age, stage, MYCN genomic content and DNA ploidy index. Twenty seven children were < 1 year (yr), 13 presented with stage I and II, 7 with stage IV-S, 17 with stage III and 47 (56%) with stage IV. Tumor specimens were obtained from involved bone marrow (n = 12) or surgical primary tumor specimens (n = 72). MDR1 gene expression was measured by Northern hybridization technique and expressed in arbitrary units (a. u.) (Goldstein et al., 1989). Analysis of MYCN genomic content and DNA ploidy index were performed by Southern blot hybridization technique and flow cytometry, respectively. Out of 84 tumor specimens 19 (23%) showed MYCN amplification (> 3 copies/haploid genome). In 24 cases (29%) no detectable MDR1 gene transcript was found (0 a.u.) whereas 42 (50%) had a value in the range 1-30 a.u., and 18 (21%) a value beyond 30 a.u.. High transcript levels were found in localized as well as in metastatic NB (NS). No significant correlation between MDR1 gene expression, age, stage, or MYCN genomic content was found In univariate analysis stage IV, age > 1 yr, MYCN amplification, diploid DNA content and high MDR1 gene transcript levels were significantly related to an increased risk of death. In multivariate analysis only stage IV, MYCN amplification and MDR1 overexpression remained significantly associated with an increased risk of death.(ABSTRACT TRUNCATED AT 250 WORDS)
Bénard
J
J
Laboratory of Molecular and Clinical Pharmacology, Institut Gustave Roussy, Villejuif, France.
Bourhis
J
J
de Vathaire
F
F
Ferrandis
E
E
Terrier-Lacombe
M J
MJ
Lemerle
J
J
Riou
G
G
Hartmann
O
O
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D016259:Genes, myc; D006801:Humans; D007223:Infant; D015999:Multivariate Analysis; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D011003:Ploidies; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D015996:Survival Rate
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger