Elevated Serum Levels of IGF- binding protein 2 (IGFBP-2) in patients with non-seminomatous germ cell cancer - Correlation with tumor markers Alpha-Fe

Alterations of the IGF-system have been described in different types of cancer. However, no information is available about the role of the IGF-system in patients with non-seminomatous germ cell cancer.

Free IGF-I, IGF-II, acid-labile subunit and IGFBP-1 to -4 were analyzed by specific radioimmunoassays in 32 patients with untreated non-seminomatous germ cell cancer and compared to IGFBP-levels of 38 healthy controls. Serum-IGFBPs were analyzed by western ligand- and imuno - blotting. In 16 patients, IGFBP-profiles were measured before, during and after treatment.

In patients with non-seminomas, IGF-II levels were on average 1.44-fold higher than in the healthy control group (1027±48 vs. 711±30 ng/ml, P<0.0001). IGFBP-2 levels were on average 2.6 - fold higher (586±58 ng/ml vs. 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 the decrease of the tumor markers Alpha Fetoprotein (AFP) and Human Chorionic Gonadotropin (HCG). Additionally, in all patients with recurrent disease, a significant further increase of IGFBP-2-levels (from 358±97 ng/ml to 976±260 ng/ml) was detected. IGFBP-3 levels, as measured by RIA, were not different in patients with testicular cancer compared to controls. However, WLB-analysis demonstrated markedly decreased intact IGFBP-3 bands in untreated patients and a significant increase after successful therapy.

Our results demonstrate markedly elevated IGF-II and IGFBP-2 serum levels in non-seminoma patients, 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.