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Annals of Oncology Advance Access originally published online on March 10, 2009
Annals of Oncology 2009 20(9):1582-1588; doi:10.1093/annonc/mdp038
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© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

sarcomas

Insulin-like growth factors and insulin-like growth factor-binding proteins in relation to disease status and incidence of hypoglycaemia in patients with a gastrointestinal stromal tumour

B. Rikhof1, J. van Doorn2, A. J. H. Suurmeijer3, M. W. Rautenberg4, P. J. T. A. Groenen5, M. A. J. Verdijk5, P. L. Jager6, S. de Jong1, J. A. Gietema1 and W. T. A. van der Graaf7,*

1 Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen
2 Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht
3 Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen
4 Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht
5 Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
6 Department of Nuclear Medicine, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada
7 Department of Medical Oncology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

* Correspondence to: Dr W. T. A. van der Graaf, Department of Medical Oncology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Tel: +31-24-3610353; Fax: +31-24-3540788; E-mail: W.vanderGraaf{at}onco.umcn.nl.

Objective: Patients with a gastrointestinal stromal tumour (GIST) suffering from non-islet cell tumour-induced hypoglycaemia (NICTH), being associated with increased plasma levels of pro-insulin-like growth factor (IGF)-IIE[68-88], have been reported occasionally. We studied the clinical relevance of pro-IGF-IIE[68-88] and other IGF-related proteins in GIST patients.

Patients and methods: Twenty-four patients were included. Plasma samples were collected before 1 week and median 5 months after start of treatment with imatinib, and levels of IGF-I, total IGF-II, pro-IGF-IIE[68-88], insulin-like growth factor-binding protein (IGFBP)-2, -3 and -6 were determined. GIST specimens from 17 patients and tumour cyst fluid from two patients were analysed for IGF-II and IGFBP-2.

Results: Before treatment and/or during follow-up, 3 of 24 (13%) patients showed increased plasma levels of pro-IGF-IIE[68-88]. All three developed NICTH. Overall, patients with metastatic disease, elevated serum lactate dehydrogenase activity or total tumour size >12 cm had the highest pro-IGF-IIE[68–88] levels. Most patients had increased plasma IGFBP-2 levels and these levels were significantly higher in patients with progressive disease. (Pro-)IGF-II was expressed in 82% of GISTs and IGFBP-2 only in one case.

Conclusion: We identified pro-IGF-IIE[68–88] as a marker that may be used in the surveillance of GIST.

Key words: gastrointestinal stromal tumour, IGF-II, IGFBP-2, imatinib, non-islet cell tumour-induced hypoglycaemia

Received for publication December 2, 2008. Revision received December 19, 2008. Accepted for publication January 27, 2009.


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