Circulating concentrations of IGF-I and ICFBP-3 are not predictive of incidence or clinical behavior of pediatric osteosarcoma

Background. Preclinical studies suggest a role oi insulin-like growth facto r-1 (IGF-1) in the proliferation of osteosarcoma cells in vivo. The purpose of this study is to address the relationship between serum levels oi IGF-1 and its binding protein (IGFBP-3), and the clinical behavior and outcome o i osteosarcoma in children, and to compare those levels present in osteosar coma patients with a normal population. Procedure. Serum IGF-I and IGFBP-3 levels were determined by ELISA in 37 patients with osteosarcoma treated on the same treatment regimen (OS-91 protocol), and who had available serum s amples from diagnosis. IGF-1 and IGFBP-3 levels were compared with those pr eviously established in the normal population, matched for age and gender, and were correlated with the presence of metastatic disease, histologic res ponse to preoperative chemotherapy, and event-free survival. Results. In os teosarcoma patients the median ICF-I level was 275 ng/ml (range, 105-613) a nd the median IGFBP-3 level was 3.4 mg/L (range, 2.3-5.1). IGF-1 levels dif fered from those in the normal population (P = 0.029); although we anticipa ted higher IGF-1 levels than normal children, 68% of observed standardized scores were less 0. Furthermore, IGF-1 or IGFBP-3 levels failed to correlat e with the presence oi metastatic disease (P = 0.12 and P = 0.12, respectiv ely), histologic response (Rosen-Huvos grades 3/4 vs, grades 1/2) (P = 0.95 and P = 0.71, respectively), or event-free survival (P = 0.52 and P = 0.41 , respectively). There was a strong association observed between IGF-1 and IGFBP-3 levels (P <0.001). Conclusions, In this retrospective study oi 37 p atients, we found that circulating levels of IGF-1 and IGFBP-3 a re not pre dictive of the development or clinical characteristics of pediatric osteosa rcoma. However, further studies on a larger patient population should be pe rformed in order to investigate this relationship. (C) 2001 Wiley-Liss, Inc .