Trk mRNA and low affinity nerve growth factor receptor mRNA expression and triploid DNA content in favorable neuroblastoma tumors.
Nerve growth factor (NGF) is suggested to play a role in spontaneous differentiation or regression of neuroblastoma. Expression of mRNAs for trk protooncogene and NGF low affinity receptor gene (LNGFR) were analyzed in 45 neuroblastomas with Northern Blot. Trk and LNGFR expression correlated with young age, localized tumors or IV-S disease, absence of N-myc amplification, triploid DNA content, spontaneous tumor regression and favorable prognosis. Regardless of other factors, trk and LNGFR mRNAs distinguished three prognostic subsets: one favorable (trk+, LNGFR+, n = 19, 100% survival probability), one intermediate (trk+, LNGFR-, n = 11, 62%) and one poor (trk-, n = 15, 0%). An algorithm based on the combined analysis of trk and LNGFR mRNAs and DNA ploidy divided the material in two groups with 96 and 0% survival probability respectively (p < 0.001), and predicted outcome accurately in 43 of 45 children. It is hypothesized that loss of functional NGF-receptors constitutes an early critical step in the evolution of unfavorable neuroblastomas prone to progression in spite of current therapy.
Department of Pediatrics, Karolinska Hospital and Institute, Stockholm, Sweden.
P
P
Kogner
G
G
Barbany
O
O
Björk
M A
MA
Castello
A
A
Donfrancesco
U G
UG
Falkmer
F
F
Hedborg
H
H
Kouvidou
H
H
Persson
G
G
Raschella
D004273:DNA, Neoplasm / Q000032:analysis*; D005434:Flow Cytometry; D005784:Gene Amplification; D015870:Gene Expression; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D007223:Infant; D009447:Neuroblastoma / Q000209:etiology / Q000235:genetics*; D011003:Ploidies; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000235:genetics*; D015996:Survival Rate
D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA