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Coexpression of insulin receptor-related receptor and
insulin-like growth factor 1 receptor correlates with enhanced apoptosis and
dedifferentiation in human neuroblastomas
Weber A, Huesken C, Bergmann E, Kiess W, Christiansen NM, Christiansen H
University Children's Hospital, Marburg, and. Children's Hospital, Leipzig,
Germany.
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 [PubMed - indexed for MEDLINE]
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