Elevated serum levels of IGF-binding protein 2 in patients with non-seminomatous germ cell cancer: correlation with tumor markers alpha-fetoprotein and human chorionic gonadotropin.
OBJECTIVE
Alterations of the IGF system have been described in several different types of cancer. However, no information is available about the role of the IGF system in patients with non-seminomatous germ cell cancer.


METHODS
Free IGF-I, IGF-II, acid-labile subunit, and IGF-binding proteins (IGFBPs) 1-4 were analyzed by specific RIAs in 32 patients with untreated non-seminomas and compared with IGFBP levels of 38 healthy controls. Serum IGFBPs were analyzed by western ligand blotting (WLB) and immunoblotting. In 16 patients, IGFBP profiles were measured before, during, and after treatment.


RESULTS
In patients with testicular cancer, IGF-II levels were on average 1.44-fold higher than in the healthy control group (1027+/-48 ng/ml versus 711+/-30 ng/ml, P<0.0001). IGFBP-2 levels were on average 2.6-fold higher (586+/-58 ng/ml versus 226+/-17 ng/ml, P<0.001). During follow-up, a decrease in IGFBP-2 levels was observed in all successfully treated patients, which correlated closely with a decrease in the tumor markers alpha-fetoprotein and human chorionic gonadotropin. Additionally, in all patients with recurrent disease, a significant further increase in IGFBP-2 levels (from 358+/-97 to 976+/-260 ng/ml) was detected. IGFBP-3 levels, as measured by RIA, were not different in patients with testicular cancer compared with controls. However, WLB analysis demonstrated markedly decreased intact IGFBP-3 bands in untreated patients and a significant increase after successful therapy.


CONCLUSIONS
Our results demonstrate that markedly elevated IGF-II and IGFBP-2 serum levels in patients with non-seminomatous germ cell cancer, showing a significant decrease after successful therapy and an increase in recurrent disease. Additionally, indirect evidence points to an increased proteolytic activity for IGFBP-3 in untreated testicular cancer patients.
Fottner
Christian
C
Schwerpunkt Endokrinologie und Stoffwechselerkrankungen, I. Medizinische Klinik und Poliklinik der Johannes Gutenberg Universität Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany. fottner@endokrinologie.klinik.uni-mainz.de
Sattarova
Sabina
S
Hoffmann
Kerstin
K
Spöttl
Gerald
G
Weber
Matthias M
MM
D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood; D016022:Case-Control Studies; D006063:Chorionic Gonadotropin / Q000097:blood*; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000097:blood* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D011499:Protein Processing, Post-Translational; D012008:Recurrence; D013736:Testicular Neoplasms / Q000097:blood* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D015854:Up-Regulation; D000509:alpha-Fetoproteins / Q000032:analysis*
C097353:AFP protein, human; D014408:Biomarkers, Tumor; D006063:Chorionic Gonadotropin; C515497:IGFBP3 protein, human; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D000509:alpha-Fetoproteins; D007335:Insulin-Like Growth Factor II