myelin-basic-protein and Melanoma

Neurothekeoma, a benign cutaneous lesion of probable nerve sheath origin, is divided histologically into two subtypes--myxoid and cellular. However, we believe that neurothekeoma encompasses a wider spectrum of lesions, with the myxoid and cellular subtypes falling at either end of the morphologic spectrum. Because the cellular variant of neurothekeoma sometimes resembles melanoma, it presents a difficult diagnostic problem. We report the histologic and immunohistochemical findings in 14 cases of neurothekeoma and review the findings in 35 additional cases from the literature. A detailed analysis of the histologic spectrum is also included. When examined by immunostains, only the myxoid variants of neurothekeoma stain positively for S-100 protein. We conclude that when the histological differential diagnosis is between cellular neurothekeoma and melanoma, an S-100-positive lesion should be regarded as melanoma.

Topics: Adult; Aged; Cell Nucleus; Child, Preschool; Collagen; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Male; Melanoma; Membrane Glycoproteins; Middle Aged; Mucin-1; Mucins; Myelin Basic Protein; Neoplasm Proteins; Neurothekeoma; S100 Proteins; Skin Neoplasms; Staining and Labeling; Transglutaminases

Induction of myelin genes occurs around birth in the last stage of Schwann cells differentiation and is reactivated in case of nerve injury. Previous studies showed that activation of the gp130 receptor system, using as ligand interleukin-6 fused to its soluble receptor (IL6RIL6), causes induction of myelin genes such as myelin basic protein (MBP) and myelin protein zero (Po) in embryonic dorsal root ganglia Schwann cells. We also reported that in murine melanoma B16/F10.9 cells, IL6RIL6 causes a shut-off of melanogenesis mediated by a down-regulation of the paired-homeodomain factor Pax3. The present work demonstrates that these IL6RIL6-treated F10.9 cells undergo transdifferentiation to a myelinating glial phenotype characterized by induction of the transcriptional activities of both Po and MBP promoters and accumulation of myelin gene products. For both Po and MBP promoters, a repression by Pax3 and stimulation by Sox10 can be demonstrated. Because after IL6RIL6-treatment, Pax3 disappears from the F10.9 cells (as it does in mature myelinating Schwann cells) whereas the level of Sox10 rather increases, we modulated the relative level of these factors and show their involvement in the induction of myelin gene expression by IL6RIL6. In addition, however, we show that a C/G-rich CACC box in the Po promoter is required for activation by IL6RIL6, as well as by ectopic Sox10, and identify a Kruppel-type zinc finger factor acting through this CACC box, which stimulates Po promoter activity.

Topics: Animals; Base Sequence; Blotting, Northern; Blotting, Western; Cell Differentiation; Cell Division; DNA-Binding Proteins; DNA, Complementary; Down-Regulation; Doxycycline; Early Growth Response Protein 2; Genes, Reporter; Genetic Vectors; High Mobility Group Proteins; Interleukin-6; Melanoma; Mice; Molecular Sequence Data; Mutagenesis, Site-Directed; Mutation; Myelin Basic Protein; Myelin P0 Protein; Myelin Sheath; Neuroglia; Phenotype; Promoter Regions, Genetic; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; SOXE Transcription Factors; Time Factors; Transcription Factors; Transcriptional Activation; Transfection; Tumor Cells, Cultured; Two-Hybrid System Techniques

35 intracranial tumours, 18 gliomas, 12 meningiomas, one neurilemmoma (neurinoma), one malignant melanoma and two metastases were successfully grown in-vitro and were submitted to immunocytochemical reactions, including cytokeratin, glial fibrillary acid protein (GFAP), vimentin, fibronectin, S-100 protein, neurofilament proteins, neuron-specific enolase (NSE) and basic myelin protein (MBP). Cytokeratin in metastases, GFAP and vimentin in gliomas, vimentin in meningiomas were consistently positive. S-100 protein was weakly and partially positive in gliomas, meningiomas, the neurilemmoma and malignant melanoma. Positive demonstration of fibronectin within cells was interpreted as a consequence of phagocytosis, except in meningiomas where fibronectin expression next to cell membranes seemed genuine. All other tested markers proved negative. The most important result seems to be that cells expressed markers irrespective of cellular shape and cytological morphology. It can be concluded that the cellular population as a whole consisted of tumour cells during the short time under observation and that supportive cell contamination during this early growth period was negligible.

Topics: Biomarkers, Tumor; Brain Neoplasms; Fibronectins; Glial Fibrillary Acidic Protein; Glioma; Humans; Immunohistochemistry; Intermediate Filament Proteins; Melanoma; Meningioma; Myelin Basic Protein; Neurilemmoma; Phosphopyruvate Hydratase; S100 Proteins; Vimentin

The presence of myelin basic protein (MBP) within a skin neoplasm would support its derivation from Schwann's cells, since this substance is routinely present within Schwann's cells in the peripheral nervous system. Using a monoclonal antibody prepared against MBP and an unlabeled antibody peroxidase-antiperoxidase assay, we surveyed a variety of skin lesions suspected of being derived from Schwann's cells to determine whether MBP was present. Myelin basic protein was detected within the cytoplasm of cells composing benign solitary schwannoma (neurilemmoma) and neurofibroma, confirming the association of these lesions with proliferation of Schwann's cells. Myelin basic protein was not found in a variety of intradermal and compound nevus cell nevi nor in malignant melanoma. This negative finding supports electron microscopic evidence suggesting that nevus cells have no relationship to Schwann's cells even though some nevus cell arrangements suggest Schwann's cell derivation under the light microscope.

Topics: Animals; Antibodies, Monoclonal; Histocytochemistry; Humans; Immunoenzyme Techniques; Melanoma; Mice; Mice, Inbred BALB C; Myelin Basic Protein; Neurilemmoma; Neurofibroma; Nevus, Pigmented; Skin Neoplasms; Swine

The electrophoretic mobility test (EMT) is an in vitro assay for demonstrating cellular immunity. In the presence of tumor antigens lymphocytes of tumor patients liberate lymphokines, which reduce the charge of indicator particles resulting in a measurable reduction of their eletrophoretic mobility. Lymphocytes of 174 patients were tested by EMT. The antigens used were a basic myelin protein termed encephalitogenic factor (EF) and a 3M KCl extract from melanoma tissue. In 91% of the cancer patients there was a positive lymphocyte response. In contrast to this the controls and non-malignant diseases showed a positive result in only 8.7% of the cases. Using the 3M KCl extract from melanoma tissue as tissue as antigen 1 of the benign controls, 3 patients with nonmalignant diseases and none of the 49 patients with malignant diseases reacted positively, whereas in the melanoma group 86% showed a positive lymphocyte response. The results show the possibility of demonstrating tumor specific immune reaction in the EMT.

Topics: Antigens; Antigens, Neoplasm; Female; Humans; Immunity, Cellular; Immunoelectrophoresis; In Vitro Techniques; Lymphocytes; Lymphokines; Male; Melanoma; Myelin Basic Protein; Skin Neoplasms

The specific lymphocyte sensitization of patients with malignant diseases against a basic protein, isolated from human brain, was studied by the lymphocyte migration inhibition technique. A sensitization of lymphocytes of cancer patients against this encephalitogenic factor (EF) was first reported by FIELD and CASPARY in 1970. Their test system was the Macrophage-Electrophoretic-Mobility-Test (MEMT). In 17 out of 18 patients with malignant disease we found a specific inhibition or enhancement of the migration area of lymphocytes more than 15%.

Topics: Carcinoma, Bronchogenic; Cell Migration Inhibition; Humans; Intestinal Neoplasms; Lung Neoplasms; Lymphocyte Activation; Lymphoma; Macrophages; Male; Melanoma; Myelin Basic Protein; Neoplasms; Stomach Neoplasms