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


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.


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.


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.


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

B. Rikhof, J. van Doorn, A.J. Suurmeijer, M.W. Rautenberg, P.J. Groenen, M.A. Verdijk, P.L. Jager, S. de Jong, J.A. Gietema, W.T. van der Graaf
2009; 20 (9):1582-1588
Published in: 
Annals of Oncology
Date of publication: 
September, 2009
Status of the publication: