Elias Perentes

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

SummaryThe immunoreactivity of the anti-Leu 7 (HNK-1) monoclonal antibody, a marker for natural killer cells, was evaluated with the peroxidase-antiperoxidase (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 immunoreactive cell membranes were generally those of well-differentiated tumor cells and of neoplastic cells found in tumors that usually were not embryonal in nature. Parallel immunostaining either of the same or of successive sections with an anti-glial fibrillary acidic protein serum was of considerable assistance in discriminating between different immunoreactive cells, e.g., between astrocytes and cells presumed to be oligodendrocytes.Despite its cross-recognition of cells of various histogenesis, the anti-Leu 7 monoclonal antibody can, in well-defined circumstances, elucidate specific differential diagnostic problems involving neurogenic neoplasms that cannot be resolved with routine staining techniques.

Immunohistochemical characterization of oligodendrogliomas: an analysis of multiple markers

SummaryTwenty-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 withUlex 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. Reactive astrocytes were found in the tumor, around the tumor and surrounding the supporting blood vessels. Neoplastic astrocytes were mainly found in the oligoastrocytomas and usually closely intermingled with neoplastic oligodendrocytes. GFAP-positive neoplastic oligodendrocytes were found in the typical oligodendrogliomatous areas. They had central nuclei and GFA positivity was mainly found in the perinuclear cytoplasm. They correspond to the “gliofibrillary oligodendrocytes” described by Herpers and Budka [11]. Of the oligodendrogliomas 91% displayed Leu 7 positivity, but anti-Leu 7 cannot be considered as a specific marker for oligodendrogliomas since other neuroepithelial tumors have been reported to react with this antibody [20]. MAG-, CA C- and NSE-positivities were found in a number of tumor cells in a few oligodendrogliomas. All the tumor cells were MBP-negative, but myelin sheaths and fragments of myelin in the infiltrated white matter were clearly demonstrated by this antiserum. UEA I strikingly demonstrated the vascular pattern of the tumors, and its usefulness as a discriminating marker for the supportive endothelial cells was confirmed.

Expression of epithelial membrane antigen in perineurial cells and their derivatives

SummaryParaffin-embedded surgical pathology specimens from skin (5) and muscle (2) biopsies, from Mortons 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. Our findings indicate that perineurial and Schwann cells can easily be distinguished by their different patterns of immunoreactivity with the above markers.

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

SummaryUsing 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. In two of seven pineocytomas showing neuronal or gangliogliomatous differentiation a few scattered cells displayed S-Ag positivity; two of four pineoblastomas contained small groups of strongly immunoreactive neoplastic cells; two malignant pineocytomas did not demonstrate any S-Ag immunoreactivity. Our results indicate that isolated cells in human pineal gland retain some of the cytochemical characteristics of photoreceptor cells recognized by the MAbA9-C6, and that S-Ag immunoreactivity may be occasionally expressed in pineal parenchymal tumors.

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. We did not find any morphologic or immunohistochemical evidence of glial differentiation from tumor cells that would support the concept that retinoblastoma arises from a primitive neuroectodermal cell capable of divergent differentiation along neuronal and glial lines.

Patterns of Epithelial Metaplasia in Malignant Gliomas II. Squamous Differentiation of Epithelial-like Formations in Gliosarcomas and Glioblastomas

Six cases are reported (four gliosarcomas and two glioblastomas) in which the epithelial-like areas of glial anaplasia showed focal squamous cell differentiation, characterized by the development of epithelial whorls, keratin pearls and immunopositivity for cytokeratin. The expression of glial flbrillary acidic protein and the development of squamous metaplasia usually were mutually exclusive. Autopsy findings in two patients and clinical work-up in five failed to disclose a primary extraneural malignancy. It is suggested that squamous differentiation may represent an extreme form of epithelial metaplasia in a malignant glioma. This possibility should be kept in mind in the diagnostic evaluation of such cases, especially in view of the current emphasis on the immunomorphologic demonstration of intermediate filament tumor markers.

Retinal S-antigen immunoreactivity in medulloblastomas

SummaryA series of 16 cerebellar medulloblastomas were studied immunohistochemically using a four-step immunoperoxidase (PAP) method and a monoclonal antibody (MAbA9-C6) which defines an epitope of the retinal S-antigen, a protein known to occur in retinal photoreceptor cells and pinealocytes of the pineal gland as well as in retinoblastomas, pineocytomas and pineoblastomas. Immunopositivity was demonstrated in a variable number of tumor cells in 50% of the cases. This finding may be an indication of a differentiation potential of medulloblastomas along the photoreceptor cell lineage. Alternatively, it may simply indicate the non-specificity of the retinal antigen in the neoplastic state.

GFA Protein Reactivity in Nerve Sheath Tumors: A Polyvalent and Monoclonal Antibody Study

We studied glial fibrillary acidic (GFA) protein immunoreactivity in 30 schwannomas, including two intracerebral examples, 26 neurofibromas and 12 neuromas using the immunoperoxidase method with a polyvalent antiserum (PVAS) and three well-characterized monoclonal antibody (MAb) preparations. Twelve of the schwannomas, including both intracerebral tumors, two of the neurofibromas and none of the neuromas immunostained with PVAS. Except for one schwannoma, all the PVAS-positive tumors were positive with two of the MAb preparations. While both of the intracerebral schwannomas were positive with the third MAb, none of the extracerebral tumors were. Our results suggest that: 1) human nerve sheath tumors contain cells having polypeptides that share epitopes with GFA protein, but 2) these polypeptides differ from astrocytic GFA protein by at least one epitope, and 3) the location of the tumors in relation to the central nervous system may influence GFA protein immunoreactivity.

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. In 92% of the astrocytomas and 56% of the glioblastomas variable numbers of tumor cells were positive. Some tumor cells positive for glial fibrillary acidic protein in ependymomas and astroblastomas were also CA C-positive. Schwannomas (86%), neurofibromas (100%) and meningiomas (86%) showed CA C positivity of the tumor cells, as did choroid plexus papillomas and gangliogliomas. However, all the medulloblastomas, neuroblastomas, central neurocytomas or melanomas tested in this study were entirely CA C-negative. In some examples of squamous cell carcinoma, leiomyoma, leiomyosarcoma and fibrous histiocytoma, CA C-positive neoplastic cells were also demonstrated. Our findings indicate that since various types of neoplastic and reactive cells express CA C positivity, the anti-CA C serum cannot be used as a specific marker for any tumor in human neurooncology.

Are intestinal endocrine cells affected in Hirschsprung's disease? An immunohistochemical study with anti-leu 7 monoclonal antibody*

Specimens from 15 cases of Hirschsprungs disease and 22 control cases of normal guts were studied by the peroxidase-antiperoxidase (PAP) method with with anti-Leu 7 (Leu 7) monoclonal antibody (MAb). In the normal human gut, some satellite cells in the enteric plexuses and a few nerve fibers and ganglion cells in the intestinal wall were stained with Leu 7 MAb, while endocrine cells in the intestinal mucosa showed consistent and intense cytoplasmic Leu 7 positivity. In Hirschsprungs disease, the number of Leu 7-positive endocrine cells was significantly low. The mean value of the number of Leu 7-positive endocrine cells per one microscopic field (X300 magnification) was 4.6 +/- 0.6 (+/- SE) in controls and 0.7 +/- 0.3 (+/- SE) in Hirschsprungs disease (P less than .001 by Students t test). Our findings suggest that the development of endocrine cells in the intestinal mucosa may be closely related to the development of ganglion cells in the enteric plexuses, and that the anti-Leu 7 MAb may be useful for the diagnosis of Hirschsprungs disease when biopsy specimens are limited to the mucosa only.