STUDIES ON THE IMMUNOHISTOCHEMICAL LOCALIZATION OF S-100 AND GLIAL FIBRILLARY ACIDIC PROTEINS IN HUMAN BRAIN TUMORS

Abstract

The presence and distribution of S-100 protein and glial fibrillary acidic protein (GFAP) were studied immunohistochemically in surgical and autopsy specimens from 130 human brain neoplasms. 115 cases of them were investigated in formalin-fixed paraffin embedded tissue, using the peroxidase-anti-peroxidase method, and in 37 cases cryostat sections were studied by direct immunoperoxidase or indirect immunoperoxidase method. In a case of astrocytoma immunoelectron microscopy was carried out to establish the ultrastructural localization of GFAP. The antisera raised against S-100 protein from bovine brain and GFAP from human astrocytoma in rabbits were used.Both paraffin and cryostat sections were investigated for GFA and S-100 proteins. Similar staining patterns were obtained, but cryostat sections demonstrated finer staining figures. By electron microscopy the reactive product for GFAP was found on glial filaments and diffusely throughout cytoplasm of neoplastic astrocyte.Positive immunostaining for GFA and S-100 proteins was observed in the glial neoplasms. Constituent cells of astrocytoma were found to contain S-100 protein in their nuclei and cytoplasms. GFAP was present in perikarya and processes. Rosenthal fibers and rounded granulated bodies showed different staining patterns for both protains. In malignant astrocytoma GFAP-negative small anaplastic cells were intermingled with positive neoplastic astrocytes, but some of the negative cells were stained for S-100 protein. Glioblastoma demonstrated variable immunoreactivity for both proteins from cell to cell and from case to case. In subependymal giant cell astrocytoma, most component cells stained for S-100 protein, but most of the component giant cells were negative for GFAP. In oligodendroglioma, immunoreactive material for GFAP was present in scanty cytoplasms of some tumor cells showing clear halo, and most cells were positive for S-100 protein. In mixed oligoastrocytoma a varying number of pale cells comprising area of oligodendroglioma showed similar staining pattern for GFAP. The finding suggests the presence of cells forms intermediate between oligodendroglia and astrocyte. In ependymoma, fine cytoplasmic processes forming perivascular pseudorosette were positive for both proteins, but the cells forming ependymal rosette were negative. A network of glial fibers constituting basic architecture of subependymoma was stained for both proteins, however some of the small component cells were negative for GFAP. In medulloblastoma, GFAP and S-100 protein-positive cells with processes were found around the stroma. In a case of desmoplastic medulloblastoma, cells staining for both proteins were present in pale area.In neuronal cell tumors, neuroblasts and mature nerve cells did not contain these proteins, but in a cerebral neuroblastoma S-100 protein-positive cells with long processes were found around blood vessels.S-100 protein was present in the component cells of neurilemmoma and choroid plexus papilloma. In 6 of 33 cases of meningioma, neoplastic cells contained S-100 protein, and in another 3 cases astrocytic cells with staining for both S-100 protein and GFAP were found in the stroma. Stromal cells in hemangioblastoma were negative for GFAP, although the tumor had scattered groups and fibers positive for both proteins.Osteochondroma and malignant melanoma were the other types of tumors which contained S-100 protein. Tumor cells of pituitary adenoma, craniopharyngioma, malignant lymphoma, germinoma and metastatic carcinoma did not contain either S-100 protein or GFAP.It is considered that the investigation of localization of S-100 protein and GFAP in brain neoplasms is helpful for classifying and precise identification.