Localization of neuron-specific (gamma gamma) enolase in proliferating (supportive and neoplastic) Schwann cells. An immunohisto- and electron-immunocyto-chemical study of ganglioneuroblastoma and schwannomas.

Neuron-specific (gamma gamma) enolase, a glycolytic enzyme used as a relatively specific marker for normal neurons and neuroendocrine cells, has recently been found in a variety of neoplastic cells and in reactive astrocytes. Its localization was investigated by immunohisto- and electron-immunocyto-chemistry, in the proliferating supportive Schwann cells of a peripheral ganglioneuroblastoma and in the neoplastic Schwann cells of four acoustic tumours. By light microscopy, the neoplastic Schwann cells showed moderate uneven diffuse immunopositivity for enolase.

Non-specificity of anti-carbonic anhydrase C antibody as a marker in human neurooncology.

Because the presence of carbonic anhydrase C (CA C) has been demonstrated in the oligodendrocytes of the mouse, rat and man, anti-CA C serum has been considered to be a possible specific marker for these cells. In order to determine its value in human neurooncology, specimens from 110 human tumors from the central and peripheral nervous systems as well as from five cases of cerebral infarction and two of multiple sclerosis were tested immunohistochemically by the peroxidase-antiperoxidase method with anti-CA C serum. Reactive astrocytes, oligodendrocytes in the neural parenchyma surrounding tumors, and neurons included in areas of neoplasia showed CA C immunopositivity.

Immunohistochemical characterization of human retinoblastomas in situ with multiple markers.

We studied paraffin-embedded specimens from 18 surgically enucleated eyes with retinoblastoma by peroxidase-antiperoxidase immunohistochemistry with antibodies against glial fibrillary acidic protein, S-100 protein, Leu 7 epitopes, neuron-specific enolase, the 200-kilodalton subunit of the neurofilament triplet polypeptide, and retinal S-antigen. We found that (1) glial fibrillary acidic protein, S-100 protein, and Leu 7 epitopes were detected only in well-differentiated glial cells that were interpreted as reactive and not neoplastic, (2) undifferentiated neoplastic cells expressed both neuron-specific enolase and retinal S-antigen immunoreactivity, and (3) differentiated cells forming Flexner-Wintersteiner rosettes were found to express neuron-specific enolase, retinal S-antigen, and, occasionally, neurofilament protein. These results support the view that retinoblastomas are composed of neuron-committed cells and favor the origin of these tumors from photoreceptor progenitor cells.

Expression of epithelial membrane antigen in perineurial cells and their derivatives. An immunohistochemical study with multiple markers.

Paraffin-embedded surgical pathology specimens from skin (5) and muscle (2) biopsies, from Morton's neuromas (3), traumatic neuromas (8), schwannomas (21), neurofibromas (12), and from one perineurioma and one neurothekeoma were studied by immunoperoxidase histochemistry and antibodies against epithelial membrane antigen (EMA), Leu 7 epitopes (Leu 7), S-100 protein (S-100) and cytokeratins. Normal, reactive and neoplastic perineurial cells stain consistently for EMA, whereas Schwann cells express Leu 7 and/or S-100 positivity. None of the immunoreactive cells stained for cytokeratin.

Desmoplastic supratentorial neuroepithelial tumors of infancy with divergent differentiation potential ("desmoplastic infantile gangliogliomas"). Report on 11 cases of a distinctive embryonal tumor with favorable prognosis.

Eleven cases of supratentorial neuroepithelial tumor presenting in infancy are reported. The tumors were characterized by their voluminous size, their intense desmoplasia, and the frequent presence of divergent astrocytic and ganglionic differentiation as demonstrated by special neurohistological and immunohisto- and immunocytochemical techniques. All the tumors presented in subjects below the age of 18 months, usually within the first 4 months of life.

The correlation of neoplastic vulnerability with central neuroepithelial cytogeny and glioma differentiation.

The vulnerability of neuroepithelial cells in the central nervous system (CNS) to neoplastic transformation results from the interaction of several factors: the existence of a reserve population of stem cells, the capability of differentiated cells to reenter the kinetic cycle, the number of replicating cells at risk at a particular time, the length of time during which a particular cell population remains in the cycle, the state of differentiation and the further differentiation potential of that population, and the steps of differentiation that are achieved in successive cell generations. This concept explains many aspects of CNS tumor incidence and the relationship of central neuroepithelial embryonal tumors to tumors of adult cell type. The incidence of different types of central neuroepithelial tumors can be correlated with the width of the window of neoplastic vulnerability.

Embryonal central neuroepithelial tumors: current concepts and future challenges.

While the embryonal central neuroepithelial tumors present complex conceptual and clinical problems, advances in cell type identification by special neurohistological, immunohisto- and immunocytochemical techniques have permitted discrimination of distinct cytomorphogenetic entities. These are based in part on their resemblance to the normal phases of neurocytogenesis. Four of these tumors, medulloepithelioma, desmoplastic infantile ganglioglioma, pineoblastoma and medulloblastoma, are designated as multipotential in light of their capacity to undergo divergent differentiation.

Electron-immunocytochemical localization of neuron-specific enolase in cytoplasm and on membranes of primary and metastatic cerebral tumours and on glial filaments of glioma cells.

A series of primary and metastatic human brain tumours was evaluated immunocytochemically for the electron microscopic localization of neuron-specific enolase (NSE). All contained cells which, regardless of the cell type, demonstrated an irregular distribution of NSE in their cytoplasm and on membranes. This was in contrast to the staining pattern in normal central nervous system (CNS) cells which, as previously reported (Vinores et al.

Regulation of myeloma growth in mice by antigen and regulatory idiotopes.

The effect of antigen, activation of normal A48Id+ B-cell clones, and monoclonal antibodies sharing A48-UPC10 regulatory idiotopes on the in vivo growth of spleen adapted ABPC48 myeloma cells has been examined. Immunogenic doses of bacterial levan have no detectable effects, whereas tolerogenic doses substantially delay the growth of the myeloma. The activation of normal A48Id+ B cell clones also has no apparent effect on the growth of the ABPC48 myeloma cells.

S-antigen immunoreactivity in human pineal glands and pineal parenchymal tumors. A monoclonal antibody study.

Using a four-step immunoperoxidase (PAP) method and the monoclonal antibody MAbA9-C6 (MAbA9-C6), which defines an epitope of the retinal S-antigen (S-Ag), we investigated the S-Ag immunoreactivity in human fetal, newborn, infantile and adult pineal glands and in 13 human pineal parenchymal tumors. S-Ag immunoreactivity was demonstrated in a few cells in one of the four fetal and in both infantile glands. Eight of nine adult pineal glands contained isolated MAbA9-C6-positive cells.

[Contribution of immunohistochemical methods to the study of central nervous system tumors].

The contributions of the immunoperoxidase technique for the demonstration of glial fibrillary acidic (GFA) protein, neuron specific enolase (NSE) and the Leu-7 (HNK-1) monoclonal antibody in central nervous system (CNS) tumors are reviewed. GFA protein is expressed in normal, reactive and neoplastic cells of astrocytic lineage. Its presence in nonastrocytic CNS tumors is related either to the development of gliofibrillogenesis (ependymomas), to ontogenetic factors (oligodendrogliomas; choroid plexus papillomas), or to uptake of the protein from adjacent reactive astrocytes (capillary hemangioblastomas).

Non-specific binding of mouse myeloma IgM immunoglobulins by human myelin sheaths and astrocytes. A potential complication of nervous system immunoperoxidase histochemistry.

The immunoreactivity of purified mouse myeloma IgM immunoglobulins (mouse IgM) to human myelin sheaths and astroglial cells was evaluated with the peroxidase-antiperoxidase method on paraffin-embedded tissues from human gliomas and areas of multiple sclerosis, and from normal human cerebrum, spinal cord and spinal nerve roots. The mouse IgM reacted positively with central and peripheral myelin sheaths and, as shown independently by others, with the cytoplasm of neoplastic and reactive astroglia. Parallel immunostaining of successive sections with an anti-glial fibrillary acidic protein (GFAP) serum and/or the anti-Leu 7 monoclonal antibody was of considerable assistance in identifying the immunoreactive elements and in distinguishing specific from non-specific immunostaining of myelin sheaths and astroglia.

Immunohistochemical recognition of human neuroepithelial tumors by anti-Leu 7 (HNK-1) monoclonal antibody.

The immunoreactivity of the anti-Leu 7 (HNK-1) monoclonal antibody, a marker for natural killer cells, was evaluated with the peroxidase-anti-peroxidase (PAP) method on sections of human paraffin-embedded tissues from 135 tumors of the central nervous system and five esthesioneuroblastomas. As shown independently by others, the antibody was found to react with most types of neoplastic neuroepithelial cells. Our findings indicate that the reaction is most often localized on the cytoplasmic membranes.

The malformative central nervous system lesions in the central and peripheral forms of neurofibromatosis. A neuropathological study of 22 cases.

The neuropathological features of 22 autopsied cases of NF have been reviewed, with special reference to the malformative and proliferative lesions implicating the intracranial and intraspinal neural structures. Eleven cases represented examples of the central form of the disease, and 11 examples of the peripheral form. The central form is defined by the association and multiplicity of cranial and spinal meningeal, nerve-sheath, and glial neoplasms (astrocytomas and ependymomas).

Immunohistochemical characterization of oligodendrogliomas: an analysis of multiple markers.

Twenty-eight oligodendrogliomas and seven oligoastrocytomas were immunotested by the peroxidase-antiperoxidase (PAP) method with antiglial fibrillary acidic protein (GFAP) serum, anti-Leu 7 monoclonal antibody (Mab), anti-myelin-associated glycoprotein (MAG) Mab, anti-myelin basic protein (MBP) serum, anti-carbonic anhydrase C (CA C) serum and anti-neuron-specific enolase (NSE) serum. The immunoreactivity of their vascular pattern was studied with Ulex europaeus type I lectin (UEA I). According to their morphology and distribution GFAP-positive cells were respectively interpreted as reactive astrocytes, neoplastic astrocytes and neoplastic oligodendrocytes.

The time development of direct hemolytic plaques: implications for the binding of IgM to cell surface haptens.

We studied the time development of direct hemolytic plaques in thin layers containing either sheep red blood cells (SRBC) directly haptenated (DH) with trinitrophenyl, or SRBC indirectly haptenated (IH) with dinitrophenyl coupled to human serum albumin. The DH-SRBC tend to be sparsely haptenated while the IH-SRBC tend to have very high local hapten densities. We observed marked differences in the growth of plaques for the two differently haptenated SRBC.

Simultaneous expression of glial fibrillary acidic (GFA) protein and neuron-specific enolase (NSE) by the same reactive or neoplastic astrocytes.

In normal cells of the central nervous system (CNS), glial fibrillary acidic (GFA) protein is demonstrable by immunohistochemistry in fibrillated astrocytes, and neuron-specific enolase (NSE) in neurons and their processes. However, it has been shown that NSE may also be expressed in reactive astrocytes and in various neoplastic cells of non-neuronal origin, including those of astrocytomas and glioblastomas. In the present study, a double-labelling technique using immunoperoxidase (PAP) and immunofluorescence (FITC) was employed to determine whether GFA protein and NSE could be expressed simultaneously by the same cell.