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Immunodetection of Endogenous Opioid Peptides in Human Brain Tumors and Associated Cyst Fluids¹

Laboratory of Neurobiophysics, INSERM U 318, F 38043 Grenoble, France [T. B., J-M. G. V., L. F. M., J-F. M. B., F. R. B., A. L. B.]; and Department of Neurosurgery, University of Louvain Medical School, Brussels 1200, Belgium [T. G.]

² To whom requests for reprints should be addressed, at INSERM U 318, University Joseph Fourier, CHU Albert Michallon, P. O. Box 217X, 38043 Grenoble, Cedex, France.

The antitumorigenic effects of endogenous opioid peptides and their presence in extracerebral tumors are well documented. In this study, methionine-enkephaline (met-enkephalin) was measured by radioimmunoassay in 108 glial and nonglial brain tumors and in 44 associated cyst fluids. By immunohistochemistry, the distribution of the peptide and its precursor, preproenkephalin A, was also analyzed. Met-enkephalin and preproenkephalin were detected in the cytoplasm and cell processes of all tumors. Moreover, for neuroectodermal tumors (i.e., gliomas, ganglioglio-mas, and dysembryoplastic neuroepithelial tumors), a strong inverse correlation (P < 0.0001) was observed between the met-enkephalin levels and the degree of malignancy (242.9, 148.3, 55.3, and 30.3 pg/mg protein for grade 1, 2, 3, and 4, respectively). When compared to normal tissue, this differential expression mainly results from a decrease in the opioid peptide content in high-grade neuroectodermal tumors. Meningiomas and cerebral metastases displayed low met-enkephalin levels, similar to those of grade 4 neuroectodermal tumors. Large amounts of met-enkephalin were found in all cyst fluids. These data suggest that the endogenous opioid system is an integral component of brain tumors and that met-enkephalin may represent a useful malignancy marker in neuroectodermal tumors.

¹ This work was supported by grants from INSERM, the associations ARC, LCC, FNCLC, "Espoir," and the "Region Rhone Alpes."

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 4/ 6/93. Accepted 7/27/93.