Increased expression of insulin-like growth factor I and/or its receptor in gastrinomas is associated with low curability, increased growth, and development of metastases.
OBJECTIVE
Growth factors, particularly insulin-like growth factor I (IGF-I) and IGF-I receptor (IGF-IR) in some nonendocrine and a few endocrine tumors, are thought important in recurrence, growth, and aggressiveness. Whether this is true of neuroendocrine tumors such as gastrinomas is unclear. The aim of this study was to address this question in gastrinomas.


METHODS
IGF-I and IGF-IR expression in gastrinomas from 54 patients with Zollinger-Ellison syndrome were analyzed and correlated with clinical/tumor characteristics. IGF-I and IGF-IR mRNA levels were determined by competitive reverse transcription-PCR. IGF-IR expression, assessed by immunohistochemistry, was done on a subset.


RESULTS
IGF-IR mRNA was found in 100% and IGF-I in 89%. IGF-I mRNA expression varied by >254-fold, IGF-IR by 2,670-fold, and the levels correlated in a given tumor. The IGF-IR level was lower in gastrinomas of patients who were rendered disease free and increased levels correlated with tumor growth, aggressiveness, extent, and with liver metastases. Increased IGF-I levels correlated with increased growth, tumor extent, and aggressiveness. Neither IGF-IR nor IGF-I levels correlated with tumor location, size, or its clinical/functional features. The IGF-IR correlated with disease-free survival. IGF-IRbeta was found in 31 of 32 tumors (97%) by immunohistochemistry.


CONCLUSIONS
These results indicate that IGF-I and IGF-IR are expressed in almost all gastrinomas. Furthermore, assessment of IGF-I/IGF-IR expression in gastrinomas may be clinically useful in identifying those patients with more aggressive tumors who might benefit from more aggressive treatment.
Furukawa
Masayuki
M
Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Hematopathology Section, Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland 20892-1804, USA.
Raffeld
Mark
M
Mateo
Carmen
C
Sakamoto
Akio
A
Moody
Terry W
TW
Ito
Tetsuhide
T
Venzon
David J
DJ
Serrano
Jose
J
Jensen
Robert T
RT
D000293:Adolescent; D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D018572:Disease-Free Survival; D005260:Female; D015408:Gastrinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1