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    Expression of Met protein in thyroid tumours.

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    Met protein is a transmembrane 190 kD heterodimer with tyrosine kinase activity, encoded by c-MET oncogene. It serves as a high affinity receptor for hepatocyte growth factor (HGF)/scatter factor (SF), a cytokine which stimulates cell proliferation, motility, and invasion. Expression of Met protein was investigated in 116 thyroid tumours using an anti-Met mouse monoclonal antibody (DQ-13) active on paraffin-embedded material. Reactivity for DQ-13 was observed in 77 per cent of papillary carcinomas, in 70 per cent of Hürthle cell tumours, and rarely in other tumours. The staining was either uniformly present throughout the tumour or limited to nests of infiltrating tumour cells. In some Hürthle cell tumours, prominent accumulation of the protein was observed in the Golgi area. Reactivity for Met protein was decreased or absent in poorly differentiated tumours and was not influenced by tumour size, presence of lymph node metastases, or age of the patient. Immunostaining for Ki-67 revealed that cytoplasmic accumulation of Met protein was not associated with enhanced proliferation of tumour cells. Overexpression of Met protein in thyroid papillary carcinoma may result in increased motility of tumour cells, which in turn may account for intraglandular multifocal dissemination and early lymph node metastasis

    Immunoreactivity for IL-1 beta and TNF alpha in human lymphoid and nonlymphoid tissues.

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    Monoclonal antibodies (MAbs) against two non-cross-reacting antigens of human IL-1 beta (Vhp20 and BRhC3) and human TNF alpha (B154.2 and B154.7) were applied to identify cytokine-containing cells in tissue sections and in cell suspensions. IL-1 beta- or TNF alpha-positive cells were not present in immunostained cytocentrifuge smears prepared from freshly isolated peripheral blood leukocytes, spleen, and lymph node cells. After 18 hours of culture with bacterial endotoxin (LPS), 80% to 90% of blood monocytes, 30% of spleen macrophages, and 2% to 28% of lymph node macrophages were strongly positive for IL-1 beta with either of the MAbs. Furthermore, 25% to 35% of blood monocytes and 6% to 60% of lymph node macrophages were stained for TNF alpha. Cells positive for IL-1 beta or TNF alpha were extremely rare in sections of normal thymus, spleen, and lymph nodes. Immunoreactivity for IL-1 beta or TNF alpha was frequently observed in sections of granulomatous lymphadenitis (N = 11). IL-1 beta or TNF alpha staining was confined to the epithelioid macrophages forming the granuloma, and the intensity of TNF alpha reactivity was generally stronger. The high frequency of cytokine-containing cells in this pathologic condition was confirmed in a cell suspension study showing that 20% of epithelioid macrophages were weakly positive for IL-1 beta and 80% were strongly positive for TNF alpha. The presence of cytokine-containing cells was investigated in cryostat sections of several nonlymphoid organs with normal histologic appearance. IL-1 beta reactivity was not observed in any of the tissues. TNF alpha reactivity was frequently demonstrated in isolated macrophages embedded in the interstitial connective tissue
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