Coexpression of Messenger RNA for TRK Protooncogene and Low Affinity Nerve Growth Factor Receptor in Neuroblastoma with Favorable Prognosis

Per Kogner, Gisela Barbany, Carlo Dominici, Manuel A. Castello, Giuseppe Raschellá, Håkan Persson

Research output: Contribution to journalArticle

194 Citations (Scopus)

Abstract

Nerve growth factor (NGF), essential for differentiation and survival of sympathetic neurons is suggested to play a role in differentiation or regression of neuroblastoma. Expression of mRNA for the trk protooncogene, encoding a tyrosine kinase receptor essential for functional NGF signal transduction, and mRNA for the low affinity NGF receptor (LNGFR) was examined in 45 neuroblastomas and 3 benign ganglioneuromas using Northern blot analysis. Expression of irk mRNA and LNGFR mRNA correlated with young age, favorable clinical stages, and absence of N-myc amplification. All children (n = 19) with neuroblastomas coexpressing mRNA for irk and LNGFR are alive 8-84 months from diagnosis, regardless of age and stage. In contrast, no child (n = 15) with tumor lacking irk mRNA is alive without disease. Three subsets of patients were distinguished, one favorable (trk+, LNGFR+, n = 19, 100% survival probability), one intermediate (trk+, LNGFR-, n = 11,62.3% survival probability), and one unfavorable (trk-, LNGFR +/-, n = 15, 0% survival probability, P < 0.001). In widespread neuroblastoma stage IVS prone to spontaneous regression, three tumors coexpressing irk and LNGFR mRNAs regressed after no or minimal therapy while the remaining tumor expressing irk but not LNGFR mRNA progressed to a fatal outcome. It is concluded that neuroblastomas coexpressing mRNA for both NGF receptor subtypes are favorable tumors likely to differentiate or regress spontaneously or respond to conventional therapy. It is further hypothesized that loss of functional NGF receptors is an important step in tumorigenesis of undifferentiated malignant childhood neuroblastoma. For these unfavorable tumors current therapy remains futile and first-line innovative therapy is justified. © 1993, American Association for Cancer Research. All rights reserved.
Original languageEnglish
Pages (from-to)2044 - 2050
Number of pages7
JournalCancer Research
Volume53
Issue number9
Publication statusPublished - 1993
Externally publishedYes

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kogner, P., Barbany, G., Dominici, C., Castello, M. A., Raschellá, G., & Persson, H. (1993). Coexpression of Messenger RNA for TRK Protooncogene and Low Affinity Nerve Growth Factor Receptor in Neuroblastoma with Favorable Prognosis. Cancer Research, 53(9), 2044 - 2050.