bromochloroacetic-acid and Sarcoma--Kaposi

Topics: Herpesvirus 8, Human; Humans; Immunohistochemistry; Keratins; Lymphocytes; Lymphoma, Primary Effusion; Male; Middle Aged; Sarcoma, Kaposi

Kaposi's Sarcoma (KS) is a proliferation of aberrant vascular structures lined by spindle cells, and is caused by a gammaherpes virus (HHV8/KSHV). Its course is aggravated by co-infection with HIV-1, where the timing of infection with HIV-1 and HHV8 is important for the clinical outcome.. In order to better understand the pathogenesis of KS, we have analysed tissue from two AIDS-KS lesions, and from normal skin by serial analysis of gene expression (SAGE). Semi-quantitative RT-PCR was then used to validate the results.. The expression profile of AIDS-related KS (AIDS-KS) reflects an active process in the skin. Transcripts of HHV8 were found to be very low, and HIV-1 mRNA was not detected by SAGE, although it could be found using RT-PCR. Comparing the expression profile of AIDS-KS tissue with publicly available SAGE libraries suggested that AIDS-KS mRNA levels are most similar to those in an artificially mixed library of endothelial cells and leukocytes, in line with the description of KS lesions as containing spindle cells with endothelial characteristics, and an inflammatory infiltrate. At least 64 transcripts were found to be significantly elevated, and 28 were statistically downregulated in AIDS-KS compared to normal skin. Five of the upregulated mRNAs, including Tie 1 and sialoadhesin/CD169, were confirmed by semi-quantitative PCR to be elevated in additional AIDS-KS biopsies. Antibodies to sialoadhesin/CD169, a known marker of activated macrophages, were shown to specifically label tumour macrophages.. The expression profile of AIDS-KS showed 64 genes to be significantly upregulated, and 28 genes downregulated, compared with normal skin. One of the genes with increased expression was sialoadhesin (CD169). Antibodies to sialoadhesin/CD169 specifically labelled tumour-associated macrophages, suggesting that macrophages present in AIDS-KS lesions belong to a subset of human CD169+ macrophages.

Topics: Acquired Immunodeficiency Syndrome; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Galectins; Gene Expression Profiling; Herpesvirus 8, Human; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Receptors, Immunologic; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sarcoma, Kaposi; Sialic Acid Binding Ig-like Lectin 1; Skin

The origin of spindle-shaped cells in Kaposi's sarcoma (KS) remains controversial. Non-specific histochemical reactions, electron microscopic examinations and immunostainings using antibody against factor VIII-related antigen (F VIII-RAG) and Ulex europaeus agglutinin I (UEAI) lectin as endothelial markers have given contradictory results. Immunohistochemical techniques were applied to 7 frozen skin biopsy specimen of KS from 5 elderly Mediterranean people and 1 renal allograft recipient, and a group of 27 other frozen cutaneous tumours including haemangio and lymphangiosarcomas, benign vascular lesions and various epithelial, melanocytic, fibrohistiocytic, fibrosarcomatous and muscular tumours. Using UEAI and antibodies against F VIII-RAG, HLA-DR and vimentin, a large proportion of positive KS spindle cells was found in all cases whereas cells were negative for keratin. Among the various immunoreactivity patterns observed in this study, a unique immunohistochemical profile was demonstrated for KS, angiosarcoma and endothelial cell, which strongly supports the endothelial origin of spindle cells in KS. Whereas F VIII-RAG, HLA-DR, vimentin and UEAI were sensitive endothelial markers, only F VIII-RAG appeared specific for endothelial cells since UEAI stained 2 squamous cell carcinomas and HLA-DR and vimentin were present in various mesenchymal and melanocytic tumours.

Topics: Adult; Aged; Antigens; Endothelium; Factor VIII; Hemangiosarcoma; Histocompatibility Antigens Class II; Histocytochemistry; HLA-DR Antigens; Humans; Immunoenzyme Techniques; Keratins; Lectins; Middle Aged; Plant Lectins; Sarcoma, Kaposi; Skin Neoplasms; Vimentin; von Willebrand Factor