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, 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. Electronic address: W.vanderGraaf@onco.umcn.nl.
Abstract
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.
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.
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