IMMUNODETECTION OF ENDOGENOUS OPIOID-PEPTIDES IN HUMAN BRAIN-TUMORS AND ASSOCIATED CYST FLUIDS

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