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At least 19 recordsLinked to original sources
PubMed2004

Immunohistochemical detection of human herpes virus-8 latent nuclear antigen-1 is useful in the diagnosis of Kaposi sarcoma.

Kaposi sarcoma is a low-grade vascular neoplasm that has been shown by molecular analysis to uniformly express the latent nuclear antigen-1 of human herpes virus 8. Differentiating Kaposi sarcoma from other benign or malignant vascular tumors, as well as other nonvascular spindle cell soft-tissue neoplasms, can be challenging. Thus, detection of human herpes virus 8 in fixed tissues would be diagnostically useful. Recently, a monoclonal antibody to human herpes virus 8 latent nuclear antigen-1 has become commercially available for immunohistochemical analysis. We sought to study the sensitivity and specificity of this antibody in the detection of human herpes virus 8 latent nuclear antigen-1 in Kaposi sarcoma. Fixed, paraffin-embedded tissue sections from 21 cases of Kaposi sarcoma, nine cases of spindle cell hemangioma, five cases of cutaneous angiosarcoma, five cases of dermatofibrosarcoma protuberans, one case of vascular transformation of a lymph node, four cases of pilar leiomyoma, four cases of stasis dermatitis, four cases of pyogenic granuloma, and three cases of spindled melanoma were examined immunohistochemically using the rat monoclonal antibody to human herpes virus 8 latent nuclear antigen-1, open reading frame-73 (Advanced Biotechnologies Inc.). Tissue sections were stained with automated immunostainers (Ventana) using heat-induced epitope retrieval and a standard DAB detection kit (Ventana) modified to detect rat Ab. Strong, diffuse, nuclear staining in >10% of tumor cells was considered a positive result. In all, 21/21 cases of Kaposi sarcoma showed strong, diffuse, nuclear staining for human herpes virus 8 latent nuclear antigen-1 (100%), whereas all cases of spindle cell hemangioma, cutaneous angiosarcoma, dermatofibrosarcoma protuberans, vascular transformation of lymph node, pilar leiomyoma, stasis dermatitis, pyogenic granuloma, and spindled melanoma were negative for this antigen. The monoclonal antibody to human herpes virus 8 latent nuclear antigen-1, open reading frame-73, is a highly sensitive and specific marker of human herpes virus 8 infection in paraffin-embedded tissue sections of Kaposi sarcoma. As such, it is an extremely useful tool for differentiating between Kaposi sarcoma and other vascular and nonvascular spindle cell lesions, which do not express human herpes virus 8 latent nuclear antigen-1.

Antibodies, Monoclonal↗
PubMed1990

Lymphangioscintigraphy in AIDS-associated Kaposi sarcoma.

Kaposi sarcoma, a common opportunistic neoplasm complicating AIDS, is thought to arise from the vasculature and possibly from lymphatic endothelium. To evaluate the nature and extent of lymphatic involvement in AIDS-associated Kaposi sarcoma, we used an improved technique of whole-body lymphangioscintigraphy. Six human-immunodeficiency-virus-seropositive men (40-51 years old) with AIDS and extensive Kaposi sarcoma had bilateral foot and/or hand intradermal injection of 0.05 ml of 99mTc-labeled human serum albumin (500 microCi, 18.5 MBq). After sequential whole-body scanning with a digital gamma camera, the findings were interpreted by comparing them with findings from similar studies in 30 other patients without AIDS or Kaposi sarcoma (26 with primary or secondary lymphedema and four with normal extremities). Unlike in normal limbs, where lymphangioscintigraphy displayed early lymphatic truncal and regional nodal filling with radionuclide, in patients with Kaposi sarcoma, lymphangioscintigraphy disclosed a variety of abnormal patterns with some features distinct and others resembling lymphatic dysplasia as seen in primary and secondary lymphedema. These included focal accumulation of tracer within lymphatic channels in the distribution of cutaneous Kaposi lesions; delayed tracer transport with absent, faint, or intense regional lymph nodal uptake; and retarded or impeded lymphatic drainage with tracer intensification in the region of Kaposi sarcoma plaques. The impaired lymphatic drainage and nodal dysfunction seen on scintigrams in patients with AIDS-associated Kaposi sarcoma suggest a close connection between the lymphatic system and this disorder.

Acquired Immunodeficiency Syndrome↗
PubMed1975

Chemotherapy for advanced Kaposi sarcoma.

Kaposi sarcoma is a rare disorder, usually controlled with conservative localized treatment. However, prognosis is serious for patients with aggressive cutaneous disease, and aminous for those with visceral involvement. Two cases of advanced Kaposi sarcoma are reviewed to illustrate a chemotherapeutic approach to patients with this disease. The first case represents a verified response of visceral Kaposi sarcoma to chemotherapy. The second provides an example of the control of aggressive dermatologic disease.

Aged↗
PubMed2006

Role of environmental factors in the pathogenesis of classic and African-endemic Kaposi sarcoma.

Kaposi sarcoma (KS) is a mesenchymal tumour associated with human herpesvirus-8 (HHV-8) infection. However, the incidence of HHV-8 infection is far higher than the prevalence of KS, suggesting that viral infection per se is not sufficient for the development of aggressive phenotype and that one or more additional cofactors are required. The great geographical variation in African-endemic and classic KS incidence points to a role for environmental factors in the etiology of Kaposi sarcoma. However, there are few unequivocably established environmental factors involved in KS pathogenesis. This review focuses on the environmental factors thought to be associated with KS, more particularly iron exposure and facilitation of transmission of HHV-8 infection by contact with blood-sucking arthropods.

Africa↗
PubMed2006

Absence of Y-chromosome sequences in tumors from African women with AIDS-related Kaposi sarcoma.

Kaposi sarcoma (KS) occurs with relatively high frequency in immunosuppressed transplant recipients and in patients with AIDS. Recently, Italian investigators reported transplant-related KS tumors bearing donor-derived antigens, suggesting possible parenteral transmission of KS as whole cells, i.e., chimeric tumors. To investigate the hypothesis that KS whole cells may also be transmitted into immunocompromised persons via heterosexual acts, we tested nodular KS lesions and matched normal tissue obtained from female patients with AIDS for the presence of the Y-chromosome specific sex determining sequence (SRY). Among 25 unique tumors tested, none was positive for SRY sequence. While our results do not exclude sexual cellular transmission of whole KS cells, they suggest that if it occurs, it is rare.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Role of scatter factor in the pathogenesis of AIDS-related Kaposi sarcoma.

Kaposi sarcoma (KS) is a complex multicellular neoplasm that is commonly associated with AIDS. The pathogenesis of KS is not well understood. KS tumor cells grow poorly in vitro and require medium conditioned by retrovirus-infected T lymphocytes. We observed that conditioned medium (CM) from type II human T-cell leukemia virus (HTLV-II)-infected T cells (HTLV-II CM) induces conversion of endothelial cells (ECs) to a KS tumor cell-like phenotype. ECs grown in HTLV-II CM acquired a spindle-shaped morphology, the ability to express factor XIIIa and other KS cell markers, and a cytokine production profile similar to that of KS cells. We found that HTLV-II CM contains large quantities of scatter factor (SF), an angiogenic cytokine that stimulates cell motility. SF induced ECs to become spindle-shaped and express factor XIIIa. Moreover, SF was found to be a mitogen for KS cells in vitro and was identified within KS lesions in vivo. SF mRNA was present in KS cells in vitro, and antibodies against SF inhibited the growth of KS cells. The receptor for SF, the c-met protein, was expressed by ECs, dermal dendrocytes, and KS tumor cells in vitro and in vivo. HTLV-II CM was highly angiogenic in vivo, which was blocked by antibodies against SF. Based on these findings, we suggest that SF plays a role in the initiation and maintenance of KS lesions.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Vascular endothelial growth factor/vascular permeability factor is an autocrine growth factor for AIDS-Kaposi sarcoma.

Kaposi sarcoma (KS) is the most common tumor associated with HIV-1 infection and develops in nearly 30% of cases. The principal features of this tumor are abnormal vascularization and the proliferation of endothelial cells and spindle (tumor) cells. KS-derived spindle cells induce vascular lesions and display enhanced vascular permeability when inoculated subcutaneously in the nude mouse. This finding suggests that angiogenesis and capillary permeability play a central role in the development and progression of KS. In this study, we show that AIDS-KS cell lines express higher levels of vascular endothelial growth factor/vascular permeability factor (VEGF/VGF) than either human umbilical vein endothelial cells or human aortic smooth muscle cells. AIDS-KS cells and primary tumor tissues also expressed high levels of Flt-1 and KDR, the receptors for VEGF, while the normal skin of the same patients did not show any expression. We further demonstrate that VEGF antisense oligonucleotides AS-1 and AS-3 specifically block VEGF mRNA and protein production and inhibit KS cell growth in a dose-dependent manner. Furthermore, growth of KS cells in nude mice was specifically inhibited by VEGF antisense oligonucleotides. These results show that VEGF is an autocrine growth factor for AIDS-KS cells. To our knowledge, this is the first report that shows that VEGF acts as a growth stimulator in a human tumor. Inhibitors of VEGF or its cognate receptors may thus be candidates for therapeutic intervention.

AIDS-Related Opportunistic Infections↗
PubMed2006

Detection of HHV-8 in pyogenic granuloma-like Kaposi sarcoma.

Kaposi sarcoma (KS) is a low-grade vascular neoplasm associated with human herpesvirus-8 (HHV-8) infection. Clinically, lesions commence as blue-red macules that may develop into plaques and eventually into nodules. The histologic appearance spans a broad spectrum and varies with the stage of the lesion. At each stage, KS has significant morphologic overlap with other vasoproliferative lesions. Recently, we encountered 6 KS tumors that histologically mimicked pyogenic granuloma (PG), a common benign vascular tumor of the skin that usually does not figure in the histologic differential diagnosis of KS. We stained 6 PG-like KS and 28 PGs with a mouse monoclonal antibody (13B10) against HHV-8 latent nuclear antigen-1 (LNA-1) to determine the utility of immunoperoxidase staining in distinguishing KS from PG. All 6 PG-like KS demonstrated nuclear staining for HHV-8 LNA-1. No staining was identified in any of the 28 PGs. Histologic criteria often used to differentiate between these two entities were not helpful in our cases. The only distinguishing feature was the presence or absence of HHV-8 LNA-1 staining. The presence of HHV-8 LNA-1 nuclear staining seems to be a specific marker for KS when comparing PGs and PG-like KS. Immunoperoxidase staining for HHV-8 LNA-1 is a useful diagnostic tool in this setting.

Adult↗
PubMed2000

Update on the pathogenesis and treatment of Kaposi sarcoma.

Kaposi sarcoma (KS), an unusual tumor of vascular origin, was one of the first recognized manifestations of AIDS. In the past few years, it has become clear that human herpesvirus-8 (HHV-8) is critical to the development of KS in the setting of immunosuppression, such as that seen with HIV infection. Other genetic and environmental factors may also play a role in the pathogenesis of KS. Of note, several endogenous substances elaborated by HIV-infected cells may promote angiogenesis and the growth of KS. With advances in our understanding of the pathogenesis of this tumor have come novel treatments for KS. Suppression of HIV replication has substantially decreased the incidence of KS in the western world, and treatment directed at angiogenesis or virus-induced tumorigenesis may ultimately lead to more effective control of KS. For most patients, however, standard chemotherapy, radiation therapy, topical therapies, and interferon-alpha remain the mainstays of treatment. In this review, recent advances in our understanding of the pathogenesis of KS are highlighted and a brief overview of current approaches to the treatment of this tumor is provided.

Antineoplastic Agents↗
PubMed2000

New therapies for the treatment of AIDS-related Kaposi sarcoma.

Kaposi sarcoma (KS) is the most common tumor arising in HIV-infected patients and is an AIDS-defining illness by the Centers for Disease Control guidelines. The clinical course of AIDS-related KS is highly variable, ranging from minimal stable disease to explosive growth. Recent advances in the elucidation of the pathogenesis of KS are uncovering many potential targets for KS therapies. Such targets include the processes of angiogenesis and cellular differentiation, sex hormones, and the KS herpesvirus/human herpesvirus-8. With the increasing recognition that effective antiretroviral regimens are associated with both a decreased proportion of new AIDS-defining KS cases and a regression in the size of existing KS lesions, most, if not all, KS patients should be advised to take antiretroviral drugs that will maximally decrease HIV-1 viral load. Five agents are currently approved by the Food and Drug Administration for the treatment of KS: alitretinoin gel for topical administration; and liposomal daunorubicin, liposomal doxorubicin, paclitaxel, and interferon-alpha for systemic administration. Many more agents, particularly angiogenesis inhibitors, are in early clinical development. The potential interaction between anti-KS agents and antiretroviral agents needs to be kept in mind. Virtually all patients with KS can derive benefit from the many approved and investigational agents developed through years of collaborative translational and clinical research.

Acquired Immunodeficiency Syndrome↗
PubMed2005

C-Kit (CD117) expression in AIDS-related, classic, and African endemic Kaposi sarcoma.

Kaposi sarcoma (KS) is a multicentric vascular neoplasm characterized histologically by the progressive proliferation of spindle-shaped tumor cells in all epidemiologic (AIDS-related, classic, endemic, and iatrogenic) forms. Human herpesvirus 8 (HHV8) is associated with all epidemiologic forms of KS and has been shown in vitro to induce the tyrosine receptor kinase c-kit in HHV8-infected cells. To date, c-kit immunoreactivity has not been systematically studied in KS lesions. Therefore, the aim of this study was to evaluate c-kit expression by immunohistochemistry in different proliferative stages and epidemiologic forms of KS. Archival cases of formalin-fixed, paraffin-embedded KS lesions, including 9 classic, 11 AIDS-related, and 15 African (endemic) forms at various histologic stages (5 patch, 8 plaque, 22 nodular), biopsied from different sites, were stained using immunohistochemistry with antibodies to HHV8 (LNA-1) and c-kit (CD117). C-kit immunoreactivity of lesional cells was demonstrated in 15 (43%) cases overall. A total of five (56%) classic, five (45%) AIDS-related, and five (33%) endemic KS cases were positive for c-kit. There was no difference in the intensity of c-kit staining between the different epidemiologic groups and histologic stages of KS. HHV8 (LNA-1) immunoreactivity was present in all (100%) classic, 10 (91%) AIDS-related, and 9 (60%) endemic cases. LNA-1 staining was demonstrated in 13 (93%) of the c-kit-positive and 15 (75%) of the c-kit-negative KS lesions. These findings indicate that c-kit expression in lesional cells can be detected by immunohistochemistry in different epidemiologic forms and histologic stages of KS. Furthermore, the expression of c-kit does not correspond with the presence of HHV8 (LNA-1) immunoreactivity in KS lesions.

Adult↗
PubMedDate not supplied

Imaging manifestations of Kaposi sarcoma.

Kaposi sarcoma (KS) is a low-grade vascular tumor that typically manifests as one of four variants: classic KS, endemic (African) KS, iatrogenic (organ transplant-related) KS, or acquired immunodeficiency syndrome (AIDS)-related KS. Several clinical and epidemiologic differences have been noted among these variants. Classic KS and endemic KS rarely require radiologic evaluation due to their usually chronic course and stability of skin compromise. However, iatrogenic KS and AIDS-related KS, the most common forms of the disease, are frequently disseminated or symptomatic and may thus require imaging studies for both diagnosis and staging. KS is the most common tumor among AIDS patients, affecting a high percentage of these individuals, and is considered to be an AIDS-defining illness. Multiple organs can be involved by AIDS-related KS. KS has been linked with human herpes virus type 8 infection and other cofactors. Although pulmonary, gastrointestinal, and skin involvement by KS has previously been described, this tumor can affect multiple organs, generating a wide spectrum of imaging findings and pathologic correlates. It is important for the radiologist to be familiar with this spectrum of imaging manifestations and corresponding pathologic findings.

Humans↗
PubMed1995

Dermatological management of Kaposi sarcoma.

Kaposi sarcoma (KS) is a chronic wound care problem for health care providers. Management of KS includes topical, intralesional, and systemic treatment modalities. The type of treatment used for KS depends on the classification of the disease which can be classical KS, African or endemic KS, iatrogenic immunosuppression KS, and epidemic or AIDS KS.

Adult↗
PubMed2005

A common genetic variant in FCGR3A-V158F and risk of Kaposi sarcoma herpesvirus infection and classic Kaposi sarcoma.

Associations of FCGR3A among men with HIV/acquired immunodeficiency syndrome suggest that host responses affect the pathogenesis of Kaposi sarcoma herpesvirus (KSHV) infection and risk of acquired immunodeficiency syndrome-associated Kaposi sarcoma. Using DNA from two HIV seronegative case-control populations in Italy, we examined whether the functional FCGR3A-V158F variant was associated with risk of KSHV infection or classic Kaposi sarcoma (CKS). In population I, we examined FCGR3A variants and risk of KSHV infection in 34 KSHV latent nuclear antigen (LANA)-seropositive and 120 LANA-seronegative adults from Sardinia (52% male; median age, 45 years; range, 31-60), whereas in population II, we examined risk of CKS from 133 CKS cases and 172 KSHV LANA-seropositive controls from Sicily, Rome, and Naples (70% males; median age, 74 years; range, 29-91). FCGR3A variants were determined by direct sequence analysis of a nested PCR of genomic DNA assay using allele-specific primers. KSHV LANA was determined by immunofluorescence assay. Overall, compared with the 158F allele, 158V was overrepresented among controls from both Mediterranean populations (frequency = 0.52 and 0.51, respectively). After controlling for age, 158V homozygous women were at increased risk of KSHV infection and CKS compared with 158F homozygous women [odds ratio (OR), 8.7; 95% confidence interval (95% CI), 0.8-98 and OR, 3.8; 95% CI, 1.0-14, respectively], whereas homozygous men were at decreased risk (OR, 0.4; 95% CI, 0.1-2.3 and OR, 0.4; 95% CI, 0.2-0.8, respectively). Significant gene-dose effects were observed among men and women at risk for CKS (P(trend) < or = 0.05). Our findings suggest that gender differences could possibly modify the effect of FCGR3A on risk of KSHV infection and CKS. Additional studies are required to confirm these relationships and determine their etiologic significance.

Adult↗