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Biomedical subjects

M Huszar

Publications and source records attributed to M Huszar.

49 records · Page 3Linked to original sources

Immunofluorescent localization of intermediate filament subunits for the differential diagnosis of malignant melanoma.

Intermediate filament subunits in normal cells and in their malignant derivatives can be used as specific markers for their histogenetic origins. We have studied five neoplasms of the skin in which positive identification of vimentin containing intermediate filaments by indirect immunofluorescence microscopy helped to establish the diagnosis of malignant melanoma. All of the neoplasms included in this study posed problems in differential diagnosis by conventional light microscopy and yielded equivocal results by conventional histochemistry. Thus, definitive distinction between poorly differentiated carcinoma and poorly differentiated melanoma could not be made by conventional microscopy. In all of the neoplasms described here, immunolabeling with antibodies against different intermediate filaments demonstrated positive staining for vimentin only. This intermediate filament subunit is present in melanocytes (as well as in many mesenchymal cells) but not in epithelial cells. Our study indicates that this technique may be valuable in differential diagnosis of malignant melanoma, particularly in instances where cells lack melanin or show other atypical morphologic features.

Aged↗

Coexpression of neuroendocrine markers and epithelial cytoskeletal proteins in bronchopulmonary neuroendocrine neoplasms.

Neuroendocrine (NE) neoplasms of the human bronchopulmonary tract were examined by electron microscopy, immunocytochemistry, and gel electrophoresis of cytoskeletal proteins from microdissected tissue samples. All samples (carcinoids, well-differentiated NE carcinoma, NE carcinomas of intermediate type, NE carcinomas of the small cell type) contained significant numbers of cells that immunostained for one or more of the following neuroendocrine markers tested: bombesin, calcitonin, ACTH, leu-enkephalin, gastrin, serotonin, somatostatin, alpha-melanocyte-stimulating hormone, vasoactive intestinal peptide, glucagon, insulin, substance P, and neuron-specific enolase. Electron microscopy revealed typical NE cell features, including variable abundant and frequently heterogeneous neurosecretory granules. Tumor cells contained filaments specifically stained with different conventional and monoclonal antibodies to cytokeratins and displayed punctate plasma membrane staining with antibodies to desmoplakins, in agreement with the electron microscopic demonstration of tonofilament bundles and desmosomes. Immunocytochemistry for NE markers and cytoskeletal proteins on consecutive sections revealed both cytokeratins and neuroendocrine substances in single cells. Using gel electrophoresis of cytoskeletal proteins of tissue regions extracted with high salt buffer and detergent, we could detect, in the tumors tested, appreciable amounts of cytokeratin polypeptides 8, 18, and 19, i.e., major cytokeratins also found in certain other lung carcinomas such as adenocarcinomas. Tumor cells were not significantly stained with antibodies to other intermediate filament proteins such as vimentin, desmin, glial filament protein, and neurofilament protein. The results show that NE substances can be synthesized in cells containing a typical epithelial cytoskeleton, i.e., cytokeratin filaments and desmosomes. These findings support the notion of an epithelial character of these tumors and appear in contrast with recent reports that neurofilaments are the only type of intermediate filaments present in carcinoids and other pulmonary NE tumors. These observations may have important implications for the histogenesis of NE carcinomas and for diagnostic pathology.

Adrenocorticotropic Hormone↗

Trabecular carcinoma of the skin. A histopathological study of two cases.

The first two cases of trabecular carcinoma of the skin reported in Israel are presented. On light microscopy, the tumors demonstrated a distinctive trabecular pattern, with cords of tumor cells embedded in the connective tissue stroma in the dermis. Dense-core neurosecretory granules, in association with formed desmosomes, were demonstrated by electron microscopy. This tumor may be misdiagnosed as lymphoma or metastatic anaplastic carcinoma, and awareness of its distinctive morphological features is necessary in order to arrive at the correct diagnosis.

Adenocarcinoma↗

Distinctive immunofluorescent labeling of epithelial and mesenchymal elements of carcinosarcoma with antibodies specific for different intermediate filaments.

A carcinosarcoma of the lung, as well as the paratracheal lymph nodes from the same patient, were subjected to immunofluorescent labeling with antibodies to tissue-specific intermediate-filament subunits, including desmin, vimentin, and prekeratin. Within the tumor mass two distinct populations of malignant cells were found: prekeratin-positive cells, corresponding to the carcinomatous component of the tumor, and vimentin-positive cells, corresponding to the sarcomatous elements. Tumor cells were also detected in lymph node metastases in which only the prekeratin-containing carcinoma cells were found. In view of the strict specificity of antivimentin and anti-prekeratin for cells of mesenchymal or epithelial origin, respectively, it is proposed that the two components of the carcinosarcoma are derived from distinct cell types and are not morphologic variants of the same tumor.

Carcinosarcoma↗

Use of antibodies to intermediate filaments in the diagnosis of metastatic amelanotic malignant melanoma.

Immunofluorescent staining of tissue from a lung tumor detected 12 years after excision of a primary malignant melanoma of the skin was negative for prekeratin and positive for vimentin, indicating that the tumor was not epithelial in origin and excluding carcinoma from the differential diagnosis. Complementary conventional staining with hematoxylin-eosin confirmed the melanocytic origin of the tumor, indicating that it was probably an amelanotic metastasis of the original malignant melanoma. The findings in this case demonstrate the potential usefulness of immunohistochemical microscopic characterization of specific intermediate filament proteins in the diagnosis of otherwise ambiguous cases of amelanotic melanoma.

Antibodies↗

Sensitivity to thermochemotherapy of AKR lymphoma and B16 melanoma variants of malignancy.

Drug resistance, which so often accompanies tumor progression, has been shown to be related to changes in membrane properties which may result in decreased drug accumulation in the tumor cell. A correlation between sensitivity to thermochemotherapy and degree of malignancy was found in the AKR lymphoma system. Hyperthermia increased adriamycin (ADR) uptake and concomitantly its cytotoxicity to AKR lymphoma cells. Moreover, these effects were more pronounced on a variant of high malignancy (HM) than on a low malignancy (LM) one. Fluorescent microscopy, as well as cytofluorometry, indicated that lymphoma cells treated by ADR at 43 degrees C were more permeable to the cytotoxic agent than those exposed to the chemotherapeutic substance at 37 degrees C. Cytofluorometry indicated the presence of a minor cell subpopulation with low ADR uptake in the HM variant, not found in the LM one. Fluorocytometry also showed that the temperature-dependent increased ADR uptake was more marked in the HM than in the LM variant, explaining the differential effect of thermochemotherapy on the two lymphoma variants. However, correlation between degree of malignancy and sensitivity to thermochemotherapy is not a general feature. In contrast to the results obtained in the AKR lymphoma system, in the B16 melanoma the low malignancy variant, F1, was more markedly affected by the combined treatment than the F10 variant. The increased cytotoxic effect of ADR by supranormal temperatures in the F1 variant was shown to be due to an augmented drug uptake. The results suggest that drug resistance in late stages of tumor progression can be overcome by an agent acting on the cell membrane. However, the data also indicate the necessity of assaying cancer treatment modalities, including those designed to circumvent drug resistance, on various tumor system models.

Animals↗

Dermatomyositis following the diagnosis of ovarian cancer.

We present a case history of a woman who developed dermatomyositis following the diagnosis of stage IV ovarian cancer. Dermatomyositis is a rare paraneoplastic syndrome that usually precedes the diagnosis of ovarian cancer by several months or years. Ours is the fifth reported case of dermatomyositis after an established diagnosis of ovarian cancer in the literature.

Aged↗

Expression of apoptosis and apoptosis-related proteins in microvessels of human ovarian epithelial tumors.

We performed an immunohistochemical analysis of apoptosis and the expression of apoptosis-related proteins (ARP) such as Fas and Fas ligand (FasL), bcl-2 and p53 in human ovarian epithelial tumors. Fas and FasL were abundant in endothelial cells of microvessels, and were observed, at times, in the myocytes of small arteries and veins, in parietal or in obstructive thrombi and fibroblasts. Apoptosis was also noticed in the endothelial cells of capillaries and sinuses. The expression of bcl-2 or p53 was rare. We found that the progression of tumor development was accompanied by considerable changes in the microvessels of ovarian tumors. These changes are probably related to the effect of ARP that are expressed by tumor epithelial cells, lymphocytes and macrophages. We suggest that the ARP are released as a result of necrosis of these cells and are taken up by cells of microvessels and by the cellular remnants of blood clots. The effect of tumors on the microvasculature can be regarded as an angiopathy that results in necrosis and hemorrhage within the tumoral tissue and enhances the progression of the malignancy.

Adult↗

A community-based cohort of 201 consecutive patients with primary Sjögren's syndrome in Israel: Ashkenazi patients compared with those of Sephardic descent.

OBJECTIVE: To determine the spectrum and prevalence of the varied manifestations, associated conditions and laboratory abnormalities of patients with primary Sjögren's syndrome in Israel and compare them between individuals of Sephardic and Ashkenazi descent and with data from the literature. METHODS: A retrospective study of a cohort of 201 consecutive patients diagnosed and followed at a single academic medical center. All cases were diagnosed using stringent criteria according to the American European Concensus Group including a labial minor salivary gland biopsy in all cases. RESULTS: Patients' mean age was 57 years and 84% were women. Overall, more than 98% of patients had sicca symptoms of dry eyes and mouth. About 35% of the cohort had hematological manifestations--primarily immune cytopenias, protein immunoelectrophoresis abnormalities and lymphoma. About 20% had associated neurological conditions (not only peripheral but often central nervous system) and 15% had pulmonary involvement. In addition, thyroid disease, liver disease, vascular or cutaneous manifestations, synovitis, ocular and renal disease could be found. In fact, the presenting manifestation was extraglandular or an abnormal test result in 39% of the patients. CONCLUSION: No significant differences were found in glandular or extraglandular manifestations or laboratory test results between Ashkenazi and Sephardic patients, despite their genetic differences. A negative history of sicca symptoms effectively rules out primary Sjögren's syndrome in this cohort. These symptoms may not be volunteered by patients and the large variety of extraglandular involvement patterns and associated conditions observed may dominate the patient's presentation, and mandate physicians' awareness and a high index of suspicion for a timely diagnosis.

Academic Medical Centers↗