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Elevated Serum Levels of IGF- binding protein 2 (IGFBP-2) in patients with non-seminomatous germ cell cancer - Correlation with tumor markers Alpha-Fetoprotein (AFP) and Human Chorionic Gonadotropin (HCG)

F Christian, Schwerpunkt Endokrinologie und Stoffwechselerkrankungen, Medizinische Klinik und Poliklinik der Johannes Gutenberg Universitaet Mainz, Mainz, Germany
s Sattarova, Schwerpunkt Endokrinologie und Stoffwechselerkrankungen, Medizinische Klinik und Poliklinik der Johannes Gutenberg Universitaet Mainz, Mainz, Germany
K Hoffmann, Schwerpunkt Endokrinologie und Stoffwechselerkrankungen, I. Medizinische Klinik und Poliklinik der Johannes Gutenberg Universitaet Mainz, mainz, Germany
G Spoettl, Medizinische Klinik II, Klinikum Grosshadern, Ludwig-Maximilians-Universitaet Muenchen, Muenchen, Germany
M Weber, Schwerpunkt Endokrinologie und Stoffwechselerkrankungen, Medizinische Klinik und Poliklinik der Johannes Gutenberg Universitaet Mainz, Mainz, Germany

Correspondence: Sabina Sattarova, Email: sabina_sattarova{at}yahoo.it

Abstract

Background/Aims: 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.

Methods: 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.

Results: 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 AFP and 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.

Conclusion: 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.