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A High Ratio of Insulin-like Growth Factor II/Insulin-like Growth Factor Binding Protein 2 Messenger RNA as a Marker for Anaplasia in Meningiomas¹

Department of Molecular Medicine, Neurogenetics Unit [A-C. S. N., M. S.], Clinical Genetics Unit [M. P., J. P. D.], Ludwig Institute for Cancer Research, Stockholm Branch, Clinical Unit and Department of Oncology-Pathology [H. P., V. P. C.], and Department of Neurosurgery [T. M.], Karolinska Hospital, Building L8:00, S-171 76 Stockholm, Sweden

Insulin-like growth factors (IGFs) I and II have been implicated as autocrine or paracrine growth promoters. These growth factors bind to specific receptors, and the response is modulated by interaction with IGF-binding proteins (IGFBPs). We observed a strong correlation between anaplastic/atypical histopathology and a high IGF-II/IGFBP-2 mRNA ratio in a set of 68 sporadic meningiomas. A strong correlation was also found between clinical outcome and IGF-II/IGFBP-2 ratio, whereas previously used histochemical markers were less correlated to outcome. We suggest that a high IGF-II/IGFBP-2 mRNA ratio may be a sign of biologically aggressive behavior in meningiomas that can influence treatment strategies. We propose that low IGFBP-2 levels in combination with increased levels of IGF-II would result in more free IGF-II and consequently greater stimulation of proliferation.

¹ This study was supported by the Swedish Cancer Foundation, the Swedish Medical Research Council, Swedish Society for Medical Research, Swedish Society of Medicine, and Stockholm Cancer Society. M. S. is the recipient of the Ireland award, a National Alliance for Research on Schizophrenia and Depression Established Investigator Award.

² To whom requests for reprints should be addressed. Phone: 46-8-51776524; Fax: 46-8-51776521.

Received 3/12/97. Accepted 5/15/97.

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