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.
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.


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.


CONCLUSIONS
We identified pro-IGF-IIE[68-88] as a marker that may be used in the surveillance of GIST.
Rikhof
B
B
Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen.
van Doorn
J
J
Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht.
Suurmeijer
A J H
AJH
Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen.
Rautenberg
M W
MW
Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht.
Groenen
P J T A
PJTA
Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Verdijk
M A J
MAJ
Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Jager
P L
PL
Department of Nuclear Medicine, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada.
de Jong
S
S
Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen.
Gietema
J A
JA
Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen.
van der Graaf
W T A
WTA
Department of Medical Oncology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. Electronic address: W.vanderGraaf@onco.umcn.nl.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D020420:Cyst Fluid / Q000737:chemistry / Q000378:metabolism; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000097:blood / Q000150:complications* / Q000473:pathology; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D015994:Incidence; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D013002:Somatomedins / Q000032:analysis*; D055815:Young Adult
D014408:Biomarkers, Tumor; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins