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Clin Cancer Res. 2003 Nov 15;9(15):5683-92.

Coexpression of insulin receptor-related receptor and insulin-like growth factor 1 receptor correlates with enhanced apoptosis and dedifferentiation in human neuroblastomas.

Author information

1
University Children's Hospital, Marburg, and. Children's Hospital, Leipzig, Germany.

Abstract

PURPOSE:

We compared the expression of the insulin receptor-related receptor (IRR) in primary human neuroblastomas with other biological and clinical parameters and the impact of its expression on prognostic outcome.

EXPERIMENTAL DESIGN:

We studied 49 neuroblastomas of different clinical stages and histological subtypes for (a) IRR, insulin-like growth factor 1 receptor (IGF-1R), TrkA, p75 neurotrophin receptor, and MYCN mRNA expression by reverse transcription-PCR; (b) MYCN gene amplification by Southern blot analyses; (c) cyclin A protein expression by Western blot analyses indicating proliferation rate; and (d) apoptotic index (AI) by terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP nick end-labeling assay.

RESULTS:

IRR mRNA expression was found in 25 (51%) neuroblastomas and correlated with stages 1, 2, 3, and 4S disease and with age </=12 months at diagnosis. IRR was expressed predominantly in neuroblastomas without MYCN gene amplification and coexpressed with IGF-1R, TrkA, and p75 neurotrophin receptor. IRR mRNA expression also correlated with an undifferentiated histology but not with the proliferation rate. In coexpression with IGF-1R, the IRR was associated with enhanced AI. IRR expression was significantly correlated with a good prognosis in all 49 neuroblastomas (6-year survival probability, 91.8% versus 49.7% for IRR nonexpression; P = 0.003).

CONCLUSION:

IRR expression is a new marker for a favorable prognosis in neuroblastoma that is independent of MYCN amplification and age at diagnosis. Our data suggest an influence of IRR on IGF signaling via IGF-1R because coexpression of these two receptor tyrosine kinases was significantly correlated with an undifferentiated histology, a high AI, and an advanced survival probability.

PMID:
14654552
[Indexed for MEDLINE]
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