INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-2 CONCENTRATIONS IN CEREBROSPINAL-FLUID AND SERUM OF CHILDREN WITH MALIGNANT SOLID TUMORS OR ACUTE-LEUKEMIA

Many tumor cell lines express insulin-like growth factors (IGFs) as au tocrine growth factors and IGF-binding protein-2 (ICFBP-2) as a major IGFBP, which, in turn, regulates the bioavailability and bioactivity o f IGFs. The aim of our study was to investigate 1) whether children wi th malignancies have elevated IGFBP-2 levels in cerebrospinal fluid (C SF) and serum, and 2) whether IGFBP-2 levels in these biological fluid s could be useful markers for the diagnosis and followup of certain tu mor types. We, therefore, measured IGFBP-2 levels in the CSF and serum of children with malignancies by Western ligand blot analysis; RIA wi th alpha IGFBP-2, a polyclonal antibody for human IGFBP-2; and immunop recipitation with alpha IGFBP-2 and alpha Hec-1 alpha, a polyclonal an tibody that recognizes IGFBP-2 and -3. Furthermore, the expression of IGFBP-2 messenger ribonucleic acid in tumor tissue from three central nervous system (CNS) tumor patients was analyzed by Northern blot anal ysis. We examined CSF from 21 children with malignant CNS tumors, 25 p atients with acute leukemia, and 4 patients with peripheral solid tumo rs and compared the IGFBP-2 levels with those in CSF from 21 patients who received a lumbar puncture to exclude meningitis. Serum was obtain ed from 7 patients with solid tumor, 12 patients with malignant CNS tu mor, and 16 patients with acute leukemia. The serum IGFBP-2 levels wer e compared to serum levels in 5 patients with sarcoma who had reached complete remission and 13 normal control children. CSF and serum were collected at the same time, before initiation of therapy. Patients wit h malignant CNS tumors showed elevated IGFBP-2 levels in CSF (P < 0.00 1), whereas patients with solid peripheral tumor or acute leukemia had normal IGFBP-2 levels in CSF. CNS tumor patients with microscopically detectable malignant cells in the CSF had the highest CSF IGFBP-2 lev els. Serum IGFBP-2 levels were increased in patients with solid periph eral tumors (P < 0.05), whereas patients in complete remission had nor mal serum IGFBP-2 levels. In summary, IGFBP-2 was elevated specificall y in CSF from patients with CNS tumor, whereas IGFBP-2 serum levels we re elevated in children with various peripheral tumors. We conclude th at IGFBP-2 in CSF could be a specific marker for malignant CNS tumors. We detected high IGFBP-2 messenger ribonucleic acid expression in 1 o f 3 CNS tumor tissues analyzed.