D2-40在Kaposi肉瘤皮损中的表达

研究^[1,2]显示,Kaposi肉瘤为内皮细胞源性,但其究竟起源于血管内皮细胞还是淋巴管内皮细胞却尚未明了.我们应用D2-40淋巴管内皮标记性抗体,同时结合其他抗体,运用免疫组化方法对新疆地区皮肤Kaposi肉瘤组织进行研究,以探讨其组织发生.     

Expression of basic fibroblast growth factor (bFGF) in Kaposi's sarcoma: an immunohistologic study

Ten cases of Kaposi's sarcoma (KS) including five AIDS-KS, one classical KS, and four pseudo-KS (acroangiodermatitis) were investigated for their expression of basic fibroblast growth factor. Antigen expression was demonstrated by immunoperoxidase staining of cryostat sections with affinity-purified anti-bFGF antibodies. It was found that bFGF was strongly expressed in basal and suprabasal keratinocytes, which were also intensively stained in normal skin biopsies. The growth factor was generally absent from the endothelial cells and spindle cells of the neoplasms. These cell types exhibited a very faint staining in a small number of lesions. The studies provide strong evidence that proliferation of KS tumor cells may not be explained by autocrine secretion mechanism of the growth factor, which has been suggested in previous reports with in vitro cultured KS cell lines.     

Cultured Kaposi's sarcoma tumor cells exhibit a chemokine receptor repertoire that does not allow infection by HIV-1

Background  

HIV-1 is known to play a critical role in the pathogenesis of AIDS-associated Kaposi's sarcoma (KS). However, it remains controversial whether KS cells are target cells for HIV infection. The aim of this study was to investigate the expression of chemokine receptors in KS cell cultures and to determine whether these cells can be infected by HIV-1.     

成纤维细胞生长因子10mRNA在脂溢性角化病皮损中的表达

目的研究成纤维细胞生长因子10 mRNA在脂溢性角化病皮损中的表达,探讨其在脂溢性角化病发病中的作用机制。方法应用原位杂交法检测FGF10 mRNA正常皮肤组织和脂溢性角化病皮损中的表达和分布。结果28例脂溢性角化病皮损表皮的全层或中下层均可见FGF10 mRNA表达(100.0%);正常皮肤表皮的基底层或个别细胞内可见FGF10 mRNA的表达(3.57%);脂溢性角化病皮损表皮中FGF10 mRNA的表达明显高于正常对照组(P<0.05)。结论FGF10 mRNA在脂溢性角化病皮损中表达增高。     

Nodular spindle cell proliferation in the wall of a varicose vein mimicking Kaposi's sarcoma

Exuberant reparative reactions resembling sarcoma have been reported in the genitourinary tract, thyroid, breast, lymph node, oral cavity and skin, but not in a varicose vein. Presented herein is the case of a 55‐year‐old man who showed an incidental nodular lesion in the wall of a varicose vein on the left leg. The nodule consisted of fascicles of spindled cells with ovoid or elongated nuclei and delicate chromatin that showed diffuse reactivity for CD31, alpha‐smooth muscle actin and D2‐40. This histopathological appearance, when coupled with extravasated erythrocytes and interstitial hemosiderin deposits, resembled Kaposi's sarcoma or spindle cell angiosarcoma. Key features helpful for recognizing that the proliferation we describe is a form of tissue repair include an association with obvious hemorrhage; lack of well‐formed curved fascicles of spindled cells; lack of intracytoplasmic hyaline globules; lack of intracellular vacuolization; cytological blandness; low mitotic count; absence of inmmunoreactivity for human herpesvirus‐8 (HHV‐8) latent nuclear antigen‐1; and absence of HHV‐8 in polymerase chain reaction (PCR) analysis. Val‐Bernal JF, Val D, Garijo MF, Gómez‐Román JJ. Nodular spindle cell proliferation in the wall of a varicose vein mimicking Kaposi's sarcoma.     

Expression of human macrophage metalloelastase (MMP-12) by tumor cells in skin cancer

Matrix metalloproteinases play an essential role in tumor growth and invasion. Different matrix metalloproteinases are often expressed in cancers with distinct patterns. To investigate the role of human macrophage metalloelastase (MMP-12) in epidermal tumors, we studied human macrophage metalloelastase mRNA and protein expression in malignant squamous cell and basal cell carcinomas, and in premalignant Bowen's disease. Human macrophage metalloelastase was detected in 11 of 17 squamous cell carcinomas in epithelial cancer cells, whereas macrophages were positive in 15 of 17 samples. In basal cell carcinomas, human macrophage metalloelastase was more often found in macrophages (seven of 19) than in cancer cells (four of 19). Human macrophage metalloelastase mRNA was also detected in three cell lines derived from squamous cell carcinomas of the head and neck and in transformed HaCaT cells, whereas premalignant tumors and primary keratinocytes were negative for human macrophage metalloelastase mRNA. Western analysis revealed human macrophage metalloelastase protein in squamous cell carcinoma cells. Our results show that human macrophage metalloelastase can be expressed in vivo and in vitro by transformed epithelial cells and indicate that the level of human macrophage metalloelastase expression correlates with epithelial dedifferentiation and histologic aggressiveness.     

Immunohistochemical analysis of procathepsin L and cathepsin B in cutaneous Kaposi's sarcoma

Background The expression of the proteinases cathepsins L and B are induced in tumors by malignant transformation, growth factors, and tumor promoters suggesting they play an important role in tumor invasion and metastasis. Methods By immunohistochemistry, procathepsin L and cathepsin B were studied in patients with Kaposi's sarcoma (KS). Formalin-fixed and paraffin-embedded tissues from 29 cases of KS (AIDS-associated KS, n= 24; non-AIDS-associated KS, n= 5) were immunolabeled with the polyclonal antibody directed against procathepsin L and the antisera directed against cathepsin B. Results Normal epidermis, eccrine sweat glands, and hair follicle expressed both cathepsins. We also found a positive staining for procathepsin L in normal blood vessels. In both “angiomatous” and “fibroblastic” lesions of KS no expression of these enzymes was observed. Conclusions These findings support the hypothesis of a benign autochthonous origin of the lesions, such as a hyperplasia.     

Soft fibroma-like lesions on the legs of a patient with Kaposi's sarcoma and lymphedema

The case of a patient who developed multiple soft fibroma-like lesions on his lower extremities affected by lymphedema and Kaposi's sarcoma is reported. To the best of our knowledge, the coexistence of these three pathologic processes is unusual and has never been described before in the literature.     

Radiotherapy of classic and human immunodeficiency virus-related Kaposi's sarcoma: results in 1482 lesions

Background The lesions of the various forms of Kaposi's sarcoma (KS), which are relatively radiosensitive, have been treated with different modalities of radiotherapy, with heterogeneous aims and results. Objective To verify the effectiveness and safety of radiotherapy on a large number of lesions endowed (classic KS) with a prolonged follow‐up. Methods A retrospective study was done on 711 lesions of classic KS and 771 lesions of human immunodeficiency virus (HIV)‐related KS, treated with traditional X‐ray therapy. Results In classic KS, a cure rate of 98.7% resulted after 13.5 years from the end of radiotherapy. In three lesions (0.42%) in the same patient, an acute radiodermatitis occurred after traumatic action. In HIV‐related KS, a complete remission was obtained in 91.43% of the lesions, partial remission in 6.74% and non‐response in 0.51% at 1 to 46 months from the end of radiotherapy. Conclusion Radiotherapy showed to be a safe and effective method, with relevant importance in the therapeutic strategy of KS.     

Transcripts of the human herpesvirus 8 genome in skin lesions and peripheral blood mononuclear cells of a patient with classic Kaposi's sarcoma

We report a 75-year-old Japanese woman with classic Kaposi's sarcoma. PCR amplified human herpesvirus 8 (HHV-8) DNA sequences from her skin lesions and peripheral blood mononuclear cells (PBMC), but not her plasma, saliva or urine. An antibody test against HHV-8 lytic antigens was positive. Immunohistochemical staining detected latent antigen. There was no evidence of HHV-8 infection in her husband, sister or daughter. Genes coding for HHV-8-encoded viral interleukin-6, viral macrophage inflammatory protein I, viral G protein-coupled receptor, viral cyclin D and viral Bcl-2 were expressed to the same degree in both her skin lesion and PBMC. Latency-associated T0.7 mRNA and HHV-8-encoded viral tegument protein genes were expressed in her PBMC at levels lower than in the skin lesions. Based on the gene expression profile, we concluded that lytic HHV-8 infection was present in her skin lesions and PBMC.     

Basement membrane and connective tissue proteins in early lesions of Kaposi's sarcoma associated with AIDS

Nearly one-third of all young homosexual men diagnosed as having acquired immune-deficiency syndrome (AIDS) develop a disseminated form of dermal Kaposi's sarcoma (KS). Although the histogenesis of KS cells is unclear, certain evidence suggests that the aberrant cells are of endothelial derivation. We have examined the presence and distribution of connective tissue-specific and basement membrane-specific macromolecules by indirect immunofluorescence and immunoperoxidase staining of frozen sections in early cutaneous lesions of KS from individuals with AIDS. The KS cells typically line the spaces between collagen bundles of the reticular dermis. When stained for the connective tissue-specific glycoprotein fibronectin, all Kaposi's sarcoma lesions showed an intense staining pattern, revealing a complex array of linear deposits of antigen that outlined the exterior surface of the collagen bundles. Antibodies to laminin and type IV collagen, both basement membrane-specific macromolecules, produced an intense staining pattern similar to that found with the anti-fibronectin antiserum, indicating that all 3 antigens are closely codistributed. In contrast, antibodies to type I collagen, the major collagen of the dermis, uniformly stained the collagen bundles in the KS lesions and in the normal control skin. Antiserum to factor VIII-associated antigen, an antigen specific to blood vascular endothelium, frequently stained the KS lesions but the staining pattern was diffuse and of variable intensity. The results suggest that KS cells are derived from the endothelium of the blood microvasculature and maintain their secretory phenotype of secreting basement membrane-specific macromolecules.     

Endemic Kaposi's sarcoma in human immunodeficiency virus type 1-seronegative persons: demonstration of retrovirus-like particles in cutaneous lesions

In 1984, Greek physicians reported on the clustering of cases of Kaposi's sarcoma (KS) on the Peloponnesus peninsula. To gain more insight into its pathogenesis, we studied the seroepidemiologic and clinicopathologic characteristics of 12 Greek KS patients (eight male/four female) five of whom were residents of an endemic area on the Peloponnesus. These patients were in good general health with ages ranging from 48 to 80 years, had no clinical signs of immunodeficiency, and combined the features of both classic and epidemic KS in that they displayed not only involvement of acral areas but also widespread mucocutaneous lesions. Routine laboratory data were within normal limits; no patient had HTLV-1 and HIV-1/2 antibodies, but all patients had antibodies to several herpesviruses. The histopathology was characteristic of KS with the peculiar feature of a dense infiltrate composed predominantly of CD4+ T lymphocytes. Immunoenzymatic/morphologic studies of the KS cells were consistent with their origin from lymphatic endothelium. Outstanding ultrastructural findings were tubuloreticular structures and cylindrical confronting cisternae, structures that are indicative of an ongoing viral infection. Indeed, extensive electronmicroscopic studies resulted in the detection of retrovirus-like particles in close association to KS cells in five of 12 patients. This in situ observation opens the possibility that this retro-virus contributes to KS development.     

硬皮病皮损中巨噬细胞游走抑制因子的表达

目的:检测巨噬细胞游走抑制因子在硬皮病中的表达.方法:免疫组化方法检测巨噬细胞游走抑制因子在20例硬皮病患者皮损中的表达,以10名正常人皮肤组织为对照.结果:硬皮病皮损中巨噬细胞游走抑制因子表达明显高于正常对照组.结论:巨噬细胞游走抑制因子表达增强可能与硬皮病的发病有关.     

Cutaneous cryptococcosis and Kaposi's sarcoma occurring in the same lesions in a patient with the acquired immunodeficiency syndrome

A 34-year-old woman presented with a history of fever, malaise and skin lesions. A diagnosis of Kaposi's sarcoma and acquired immunodeficiency syndrome (AIDS) was established, and in addition, the skin lesion which was biopsied also demonstrated cryptococcal infection. Disseminated cryptococcosis was later confirmed and the disease ran a florid course. The co-existence of different diseases within the same lesion is a feature of human immunodeficiency virus (HIV) infection, this being the third documented case of simultaneous Kaposi's sarcoma and cutaneous cryptococcosis occurring at the same site in a patient with AIDS. The nature of this co-existence is discussed with reference to the pathogenesis of Kaposi's sarcoma.     

Infection of circulating CD34+ cells by HHV-8 in patients with Kaposi's sarcoma.

Human herpesvirus type 8 (HHV-8) has been identified as the most likely candidate to be involved in the development of Kaposi's Sarcoma (KS). HHV-8 has been associated with all forms of KS, primary effusion lymphoma, and multicentric Castleman's disease and detected in various non-neoplastic cells. Its presence in cells of the different hemopoietic lineages has not yet been investigated in a comprehensive and systematic manner. In this study we searched for the presence of HHV-8 in different subpopulations of peripheral blood mononuclear cells (PBMC) from patients with classic and AIDS-associated KS, as well as from HIV-1 sero-positive and sero-negative persons without KS. Thirty-four samples of PBMC were isolated from 30 patients. Subpopulations were isolated with immunomagnetic beads. Polymerase chain reaction for HHV-8 DNA was performed on PBMC and subpopulations with a primer pair selected from ORF26 of the viral genome. Polymerase chain reaction products were subsequently Southern blotted and hybridized. In patients with KS, HHV-8 DNA was detected in nine of 11 (81%) CD19+ cells, four of 11 (36%) CD2+ cells, three of 11 (27%) CD14+ cells, and nine of 11 (81%) of the remaining depleted cell populations (DP) that contain CD34 positive cells. In a subsequent set of experiments HHV-8 DNA was detected in 10 of 12 (83%) CD34 positive cell fractions. All cell subpopulations from the non-KS group were HHV-8 negative, with the exception of one positive B cell sample obtained from an HIV-infected patient. Our data demonstrate that in peripheral blood HHV-8 is detectable not only in CD19+ cells, as previously reported, but also in other cells, including T cells, monocytes, and cells devoid of specific lineage markers. We also show for the first time that CD34+ cells in peripheral blood of KS patients are a predominant HHV-8-harboring population, suggesting that they represent an additional important reservoir for this virus in vivo.     

Sporadic, endemic and AIDS-related Kaposi's sarcoma. Different clinical course variants of the tumor demonstrated by 3 typical cases

We report on three patients suffering from Kaposi's sarcoma (KS) of the classical, endemic, and AIDS-related variant. We point out the uniformity of this tumor in terms of histomorphology. We found the characteristic findings of angiomatous structures and dense spindle cell formations. All variants of the tumor show histochemical and immunohistological evidence for a histogenesis probably from endothelial cells of venous capillaries. On the basis of our cases and the literature, we discuss to what extent cellular immunity may determine both the tumor biology and therapeutical considerations.     

Matrix metalloproteinases in the progression and regression of Kaposi's sarcoma

BACKGROUND: Matrix metalloproteinases (MMPs) are associated with Kaposi's sarcoma (KS) tumorigenesis. To date, only a few MMPs have been studied in KS lesions. Their role in KS regression has not been investigated. The aim of this study was to evaluate the expression of multiple MMPs in developing and pharmacologically regressed KS lesions. METHODS: Nine samples of acquired immune deficiency syndrome (AIDS)-related and classic cutaneous KS lesions at various histological stages were studied. Regressing KS lesions from three patients treated with systemic therapy were procured after one and two cycles of chemotherapy. Tissue sections from all specimens were immunostained using monoclonal antibodies to MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, and MMP-14. RESULTS: KS lesional cells were immunoreactive for all MMPs, except MMP-14. Admixed inflammatory cells were immunoreactive for MMP-1, MMP-2, MMP-7, MMP-9, and MMP-13. The MMP immunoprofile in residual KS lesional cells was unaltered in regressed lesions. Increased extracellular matrix (ECM) and macrophage immunoreactivity for MMPs was identified in regressed specimens. CONCLUSIONS: These data show that developing KS lesional cells express collagenases (MMP-1, MMP-13), gelatinases (MMP-2, MMP-9), stromelysin-1 (MMP-3), and matrilysin (MMP-7) but not the membrane-type MMP-14. This MMP expression profile is retained by residual KS cells and also expressed by infiltrating macrophages in regressed KS lesions. Pantanowitz L, Dezube BJ, Hernandez-Barrantes S, Tahan SR, Dabbous MK. Matrix metalloproteinases in the progression and regression of Kaposi's sarcoma.