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PubMedDate not supplied

Limb salvage surgery for primary bone sarcoma of the lower extremities: long-term consequences of endoprosthetic reconstructions.

BACKGROUND: Adjuvant chemotherapy and endoprosthetic replacement for bone sarcomas of the lower extremity is well established. The specific long-term consequences of these endoprosthetic reconstructions for the patient's affected limb are unknown. METHOD: The oncologic results and the survival of the endoprostheses were reviewed in 32 patients with primary bone sarcoma of the femur or proximal tibia. There were 26 high-grade sarcomas, and 6 low-grade sarcomas. A proximal femoral endoprosthesis was used for reconstruction in 4 patients, a total or push-through femoral endoprosthesis in 11 patients, a distal femoral endoprosthesis in 15 patients, and a proximal tibial endoprosthesis in two patients. RESULTS: Median survival was 10 years (range, 1.1 to 18.9 years) for patients with high-grade sarcoma, and 8.1 years (range, 7.1 to 10 years) for patients with low-grade sarcomas. Distant metastases developed in seven patients (22%), all with stage IIB sarcoma, with concomitant local recurrence in 3 patients (9%). Five-year overall and disease-free survival rates for high-grade sarcomas were 81% and 73%, respectively. The overall endoprosthetic survival rate was 87% at 5 years, 80% at 10 years, and 56% at 15 years. Median follow-up of the original endoprostheses was 8.3 years (range, 0.6 to 18.7 years). Endoprosthesis-related complications occurred in 13 patients (41%); most complications were mechanical failures. The highest complication rate was found in distal femoral replacements (60%); amputation was necessary in both patients treated with a proximal tibial endoprosthesis. Five endoprostheses (16%) were revised. An amputation of the involved limb was performed in four patients (13%): in two patients because of local recurrence and in the other two patients because of infection. For patients alive at follow-up, the median functional Enneking evaluation score was 22 points (range, 12 to 28 points), with the highest functional scores in patients with a distal femoral endoprosthesis, and the lowest functional scores in patients with total or push-through femoral replacements. CONCLUSION: Endoprosthetic reconstructions gave satisfying functional results in most patients after long-term survival. However, the proximal tibial and distal femoral endoprosthesis are particularly at risk for long-term endoprosthetic complications requiring additional surgical procedures.

Adolescent↗
PubMed2000

CD44 expression in soft tissue sarcomas.

Recent studies have shown that expression of alternatively splicing variants of CD44 is correlated with prognosis for several kinds of malignant tumors. However, little is known about the expression of CD44 standard and variant isoforms in soft tissue sarcomas. In this study 47 cases of soft tissue sarcoma [18 malignant fibrous histiocytomas (MFHs), 13 synovial sarcomas (SSs), 7 malignant schwannomas (MSs), and 9 liposarcomas (LSs)] were examined immunohistochemically. The monoclonal antibodies to the standard form of CD44 (CD44H) and variant exons of CD44v3, 4, 5, 6, 7, 9, and v10 were used. We analyzed the membranous expression pattern of CD44H and CD44 variant exons and assessed the relation between expression of CD44s and metastasis-free survival rates (MFSR) of patients with soft tissue sarcoma. A few sarcomas expressed CD44v3 (2/47) and v7 (2/47), but none of the sarcomas expressed CD44v10. CD44v4 (5/47), v5 (4/47), v6 (10/47), and v9 (9/47) are relatively common types of variant isoforms in soft tissue sarcomas. Expression of CD44v6 is more frequently detected in high-grade than in low-grade tumors. CD44v6 or CD44v9 expression was correlated with metastasis-free survival of patients with soft tissue sarcomas.

Adolescent↗
PubMed2002

Epithelioid sarcoma of the extremities: a dismal long-term outcome.

Epithelioid sarcoma is a rare histologic subtype of sarcoma. The clinical behavior and prognostic factors influencing survival in this disease are examined. A review of clinicopathologic features of patients with epithelioid sarcoma prospectively followed between September 1981 and April 2001 at the Cancer Institute Hospital was performed. Eight patients (4 men and 4 women) constituted the subjects of this study, with a mean age of 41 years. Tumors presented in the lower extremity in 62.5% of patients and in the upper extremity in 37.5%. All patients were followed for at least 10 years from the time of diagnosis or until death. The follow-up ranged from 17 to 228 months, with a mean of 78 months. At least one local recurrence was seen in 50% of patients. During the course of the disease, metastases to regional lymph nodes developed in 50% of patients and metastases to the lungs in 62.5%. The median survival was 31 months, with a 25% 5-year and 10-year survival rate. Pulmonary metastases were correlated with decreased survival. A delay in diagnosis of epithelioid sarcoma is common. Epithelioid sarcoma differs from other sarcoma subtypes in its propensity for nodal spread and local recurrence. Chemotherapy and radiotherapy have an insignificant effect on the course of epithelioid sarcoma. Careful follow-up, evaluating local recurrence, nodal spread, and pulmonary metastases, is warranted. The long-term outcome of epithelioid sarcoma is dismal.

Adult↗
PubMed2006

Ezrin mediates growth and survival in Ewing's sarcoma through the AKT/mTOR, but not the MAPK, signaling pathway.

Recent reports on the role of the membrane-cytoskeleton linker protein ezrin in sarcomas showed an effect on the formation of metastases, dependent on the level of ezrin expression. In this study, we explore the role of ezrin in Ewing's sarcoma, a frequently fatal mesenchymal neoplasm of children and young adults. Through both immunohistochemistry and Western immunoblot studies we find ubiquitous, high-level expression of ezrin in Ewing's sarcoma. In contrast to the observations in osteosarcoma and rhabdomyosarcoma, we demonstrate that inhibition of ezrin-mediated signal transduction, through the expression of a non-phosphorylatable T567A mutant, slows primary growth of Ewing's sarcoma cells in vitro. This reduction in growth is a result of increased apoptosis in the mutant expressing cells. We further show that expression of this mutant reduces the ability of Ewing's sarcoma cells to form experimental metastases in vivo. Molecular examination reveals that the action of ezrin in Ewing's sarcoma is dependent on the AKT/mTOR signal transduction cascade, but not MAP Kinase. These results, therefore, demonstrate that, in Ewing's sarcoma, the biology of ezrin is distinct from that described in other sarcomas. This study further validates ezrin as a potential therapeutic target.

Animals↗
PubMed2000

Uterine/female genital sarcomas.

Choosing the best management of uterine and vulvo-vaginal sarcomas depends on careful histologic review of the pathologic specimen. Prognosis and treatment vary greatly depending on specific histology, grade, and tumor stage. The initial approach to sarcomas of the female genital tract, with the occasional exception of vulvo-vaginal rhabdomyosarcoma, is surgery. Adjuvant radiation decreases local recurrence rates for uterine sarcomas, but has not been clearly shown to improve overall survival. It is frequently used as adjuvant therapy for resected high-grade or margin-positive vulvo-vaginal sarcomas, and for endometrial stromal sarcomas. Adjuvant chemotherapy has not been demonstrated to improve survival in vulvo-vaginal sarcomas, with the exception of vulvo-vaginal rhabdomyosarcomas, nor has it been demonstrated to improve survival in uterine sarcomas. Chemotherapy may be used for recurrent or persistent disease. The choice of agent depends on the histologic type of sarcoma.

Antineoplastic Agents↗
PubMed1981

Kaposi's sarcoma. Retrospective study of 90 cases with particular emphasis on the familial occurrence, ethnic background and prevalence of other diseases.

Identification of familial cases of Kaposi's sarcoma may help elucidate the role of genetic factors in this disease. To assess the prevalence of familial occurrences, the ethnic distribution of Kaposi's sarcoma and the prevalence of other diseases in our patient population, we have reviewed all cases of Kaposi's sarcoma seen at Memorial Sloan-Kettering Cancer Center between 1954 and 1975. Each patient was categorized on the basis of sex, age of onset of Kaposi's sarcoma, ethnic background, nativity, family history of Kaposi's sarcoma and prevalence of other diseases. Only one documented occurrence of familial Kaposi's sarcoma was found out of 90 cases reviewed. The frequency of familial Kaposi's sarcoma in our patient population supports the findings of other investigators. An ethnic predominance of Kaposi's sarcoma was substantiated, with most patients being immigrants from high-incidence areas (54 of 77) and predominantly of Jewish and italian heritage (52 Jewish and 17 Italian of 87).

Adult↗
PubMedDate not supplied

Soft tissue sarcomas: current trends in diagnosis and management.

Sarcomas (fleshy tumors) were distinguished from carcinoma (crab leg tumors) at the time of Hippocrates. Sarcomas are related embryologically to leukemias and lymphomas because all are thought to be malignancies of mesodermal embryologic origin. Neurosarcomas, however, are an exception, since they arise from tissue of neuroepidermal origin. Malignant sarcomas of the soft tissue represent an unusual primary malignant tumor. These lesions are characterized by their diversity in the histologic appearance and in their biologic behavior, as well as in anatomical origin. Currently there are approximately 7,400 newly diagnosed bone and soft tissue sarcomas, and approximately 4,200 deaths per year in the United States.1 The incidence of sarcomas varies by histologic type in various age groups. Embryonal rhabdomyosarcoma in the orbit peaks in the 4-year-old, and in the urinary tract in adolescence.2 Osteosarcoma has peak incidence in the teenage years, and Ewing's sarcoma develops between the ages of 15 and 30. Other sarcomas such as malignant fibrous histiocytoma and chondrosarcoma generally occur in patients aged more than 55 years. The incidence of osteosarcoma in whites and nonwhites is equal; Ewing's sarcoma is predominantly a disease of Caucasians.3 The relatively infrequent occurrence of these tumors plus their diverse histology and diverse presentations have made it difficult for any one institution to have enough patients to directly compare, in a randomized prospective fashion, one treatment with another in order to determine the optimal primary therapy. The purpose of this monograph is to review recent concepts in terms of pathology, surgery, radiation therapy, chemotherapy, and multimodality therapy.

Combined Modality Therapy↗
PubMed2005

Epithelioid sarcoma with SYT-SSX1 fusion gene expression: molecular and cytogenetic analysis.

Epithelioid sarcoma is a rare malignant soft tissue tumor of unknown histogenesis, characterized by the epithelioid morphology of tumor cells and co-expression of epithelial and mesenchymal lineage proteins. A common epithelial and mesenchymal immunophenotype is also found in another soft tissue tumor, the biphasic subtype of synovial sarcoma. Furthermore, the presence of a breakpoint at 18q11 in epithelioid sarcoma, similar to that found in synovial sarcoma, has been reported. These facts would support the hypothesis that both tumors may share a common histogenetic background. However, expression of the SYT-SSX fusion genes has been investigated in epithelioid sarcoma with negative results. We report, to our knowledge, the first epithelioid sarcoma in which the presence of SYT-SSX1 fusion gene has been detected by means of conventional RT-PCR analysis and sequencing, real-time RT-PCR and FISH. The SYT-SSX1 gene fusion was identified in a small proportion of tumoral cells. This finding supports a likely common histogenetic background for both epithelioid sarcoma and synovial sarcoma.

Adolescent↗
PubMed2006

PDGFR-alpha as a potential therapeutic target in uterine sarcomas.

OBJECTIVE: Uterine sarcomas are a heterogeneous group of tumors with a propensity for metastasis and resistance to conventional therapy. Recent success in the treatment of other solid tumors with the targeted tyrosine kinase inhibitor imatinib mesylate offers new avenues for investigation. The primary target of imatinib is c-kit, but the drug also inhibits PDGFR-alpha and PDGFR-beta. Given the lack of identified molecular targets in endometrial stromal sarcomas, leiomyosarcomas, and carcinosarcomas, the purpose of this study was to determine the protein expression of c-kit, PDGFR-alpha, and PDGFR-beta in these tumors as a preliminary step to determining their susceptibility to directed therapy. A secondary goal was to identify specific gene mutations that might be associated with activation of these proteins in uterine sarcomas. METHODS: Archived tissue from 42 cases of uterine sarcomas was stained for c-kit, PDGFR-alpha, and PDGFR-beta using immunohistochemistry. Laser-capture microdissected samples of uterine carcinosarcomas, or homogeneous areas of leiomyosarcomas or endometrial stromal sarcomas, were subjected to genetic analysis of PDGFR-alpha exons 12 and 18. RESULTS: The majority (38/42, 90%) of uterine sarcomas lacked c-kit expression and 90% (38/42) demonstrated negative or weak staining for PDGFR-beta. In contrast, 70% (30/42) of cases had strong staining for PDGFR-alpha in the tumor but not in normal myometrium or endometrium. Sequencing results revealed no mutations in exons 12 or 18 of PDGFR-alpha. CONCLUSION: c-kit and PDGFR-beta are unlikely to represent primary treatment targets in uterine sarcomas. The strong expression of PDGFR-alpha in uterine sarcoma specimens suggests a role for this receptor in tumor development, although its potential as a therapeutic target requires further investigation.

Female↗
PubMed1988

Detection of cytomegalovirus DNA in classic and epidemic Kaposi's sarcoma by in situ hybridization.

Several lines of evidence have suggested an etiologic association of cytomegalovirus (CMV) with Kaposi's sarcoma. This contention is supported by a pathoepidemiologic survey of 54 cases of acquired immunodeficiency syndrome (AIDS) at our own institution. Of the 27 patients with documented Kaposi's sarcoma, 24 (89%) showed histologic evidence of CMV infection (cytomegalic cells with viral inclusions), whereas only 9 (33%) of the patients with AIDS without Kaposi's sarcoma showed hallmarks of CMV infection. In an attempt to address this question further, we have searched for the presence of CMV nucleic acid sequences in a series of 25 patients with AIDS and Kaposi's sarcoma, using the technique of in situ DNA hybridization. The reliability of the in situ technique is demonstrated, and the technique is shown to be more sensitive than the detection of viral inclusions within Kaposi's sarcoma lesions by routine light microscopy. However, only 20% of our cases showed evidence of CMV involvement, and the CMV-positive cells within the affected Kaposi's sarcoma lesions were few and sparsely distributed. In addition, a companion series of 6 elderly patients with "classic" Kaposi's sarcoma showed no evidence of CMV infection by either conventional microscopy or in situ hybridization. These results do not support the notion of a strong association between Kaposi's sarcoma and CMV, unless the CMV sequences are present at a copy number too low for detection by these methods. The implications of these findings in light of current theories of CMV oncogenesis are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Synovial sarcoma. Inter-relationship of the biphasic and monophasic subtypes.

In order to assess minimum diagnostic criteria for synovial sarcoma, particularly the monophasic variety, and the inter-relationship between the monophasic and biphasic types, 32 examples were studied histologically, immunohistochemically (26 cases), and ultrastructurally (13 cases). Of the six biphasic synovial sarcomas examined by electron microscopy, the spindle cell component did not show evidence of epithelial differentiation or resemble the epithelial phase, but did appear fibroblastic; no tumor cells transitional between the spindle and epithelial component were evident. In contrast, all of the seven monophasic lesions had ultrastructural growth patterns and some cellular features approximating the epithelial cells of the biphasic variant. In 11 biphasic synovial sarcomas, epithelial membrane antigen was detected in the glandular epithelium of all cases and cytokeratins in eight cases; in no case were these antigens detected in the spindle cell regions of biphasic lesions. Of the 15 monophasic synovial sarcomas, two were positive for cytokeratins and four for epithelial membrane antigen. Thus, the detection of epithelial markers either immunohistochemically or by electron microscopy (or both) should be the minimal diagnostic criteria for monophasic synovial sarcomas. Based on these findings, it is suggested that monophasic synovial sarcomas do not represent the spindle cell or "stromal" phase of biphasic synovial sarcomas, but are a poorly differentiated variant of the latter. As others have suggested, these tumors are, in fact, carcinosarcomas and carcinomas of the soft tissues and the designation synovial sarcoma is inappropriate for this tumor class.

Adolescent↗
PubMed2003

Is there a role for sentinel lymph node biopsy in the management of sarcoma?

Is there a role for sentinel lymph node (SLN) biopsy in the management of sarcoma? Sentinel node biopsy has dramatically changed the management of melanoma and breast cancer, helping surgeons avoid radical lymphadenectomies in node negative patients who would previously have undergone a more morbid operation with little benefit, or remained pathologically unstaged. Many investigators have explored the use of lymphatic mapping for malignancies other than breast cancer or melanoma. Lymphatic mapping and sentinel node biopsy has not been investigated in the management of sarcomas, which is not surprising given that the majority of sarcomas spread by local extension or hematogenously. Regional lymph node metastases are rare; developing in about 3-10% of patients with localized disease. However, among certain subtypes of high-grade sarcomas there is a propensity for regional lymph node metastases. These include rhabdomyosarcoma, epithelioid sarcoma, clear cell sarcoma, synovial sarcoma, and vascular sarcomas. It is in these particular subtypes that there may be a benefit to SLN biopsy.

Humans↗
PubMed1996

Presence of human herpesvirus-like DNA sequence in oral Kaposi's sarcoma. A preliminary PCR study.

DNA sequences closely related to herpesvirus-like sequences have been found in AIDS-associated Kaposi's sarcoma. Subsequent studies indicate that these DNA sequences may be consistently found in AIDS Kaposi's sarcoma and non-AIDS Kaposi's sarcoma from different geographic regions. Oral Kaposi's sarcoma is rare and the specificity of this viral DNA in oral Kaposi's sarcoma and in other oral neoplasms has not been examined. A total of 77 oral neoplasms, including 3 Kaposi's sarcoma specimens from 2 patients with AIDS, were analyzed by polymerase chain reaction for the presence of this herpesvirus-like DNA sequence with the 330-233 primers. All three specimens of oral AIDS-Kaposi's sarcoma from two patients were positive for this DNA sequence. All of the other intraoral lesions including hemangioma, pyogenic granuloma, and various types of epithelial neoplasms, however, had negative reactions. Our results further confirm that oral Kaposi's sarcoma appears to be associated with this herpesvirus-like DNA sequence.

AIDS-Related Opportunistic Infections↗
PubMed2002

Detection of SYT-SSX fusion transcripts in archival synovial sarcomas by real-time reverse transcriptase-polymerase chain reaction.

Synovial sarcomas comprise approximately 5% of soft tissue sarcomas and occur primarily in young adults. The t(X;18) (p11.2;q11.2) has been demonstrated to be highly characteristic of synovial sarcomas, and the resulting SYT-SSX fusion transcripts have been shown to be useful diagnostic markers. We have developed a real-time, reverse transcriptase-polymerase chain reaction (RT-PCR) multiplex assay for the identification of the primary fusion transcript types (SYT-SSX1 and SYT-SSX2) from formalin-fixed, paraffin-embedded (FFPE) tissues. Twenty-nine of 30 (96.7%) histologically diagnosed FFPE synovial sarcomas were positive for the presence of either the SYT-SSX1 or SYT-SSX2 fusion transcripts. Ten of 16 (62.5%) and five of 16 (31.25%) monophasic fibrous synovial sarcomas were positive for SYT-SSX1 and SYT-SSX2, respectively. One of 16 (6.25%) monophasic fibrous synovial sarcomas was negative for either SYT-SSX fusion transcript. Twelve of 14 (85.7%) and 2 of 14 (14.3%) biphasic synovial sarcomas were positive for SYT-SSX1 and SYT-SSX2, respectively. All 13 non-synovial sarcomas tested were negative for SYT-SSX1 and SYT-SSX2 fusion transcripts. This method is a relatively simple and rapid procedure for the detection of the t(X;18)(p11.2;q11.2).

Biomarkers, Tumor↗
PubMed2005

HMGA proteins in malignant peripheral nerve sheath tumor and synovial sarcoma: preferential expression of HMGA2 in malignant peripheral nerve sheath tumor.

Histological separation of synovial sarcomas from malignant peripheral nerve sheath tumors can be difficult and available immunohistochemical markers sometimes give rise to overlapping staining patterns. Additional markers are needed to better define the two entities in the routine surgical pathology practice. To this end, we explored diagnostic applications of HMGA (HMGA1 and HMGA2) protein immunohistochemistry in comparable groups of synovial sarcoma and malignant peripheral nerve sheath tumors. The histological diagnosis of these cases was confirmed by the presence or absence of synovial sarcoma specific SYT-SSX fusion transcript analyzed by real-time reverse transcription polymerase chain reaction. In all, 13 malignant peripheral nerve sheath tumors and 15 synovial sarcomas were included in this study. Immunohistochemically, most malignant peripheral nerve sheath tumors expressed both HMGA1 and HMGA2 protein (12/13 and 12/13 cases, respectively) with moderate to strong nuclear staining patterns. Most cases of synovial sarcomas demonstrated variable expression of HMGA1. However, significant immunoreactivity for HMGA2 was present in the glandular component of a biphasic tumor (1/1) and rarely detected in monophasic synovial sarcomas (1/14). In summary, expression of HMGA2 is a feature of MPNST but not of synovial sarcoma and immunohistochemical staining of HMGA2 may be a useful marker to separate malignant peripheral nerve sheath tumor from synovial sarcoma.

Adult↗
PubMed2005

Dual-color, break-apart fluorescence in situ hybridization for EWS gene rearrangement distinguishes clear cell sarcoma of soft tissue from malignant melanoma.

Clear cell sarcoma of soft tissue (malignant melanoma of soft parts) is a soft tissue sarcoma with melanocytic differentiation that typically occurs in the tendons and aponeuroses of young adults. As demonstrated by cytogenetics and reverse-transcriptase polymerase chain reaction, between 70% and over 90% of clear cell sarcomas have a t(12;22) translocation, fusing the EWS and ATF1 genes on chromosomes 22q12 and 12q13, respectively. Identification of this translocation distinguishes clear cell sarcoma from histologic mimics, most importantly conventional malignant melanoma. We report our experience with a commercially available, dual-color, break-apart fluorescence in situ hybridization (FISH) probe, which allows detection of EWS (22q12) gene rearrangement in formalin-fixed, paraffin-embedded tissues. Histologically and immunophenotypically well-characterized cases of clear cell sarcoma (n = 10) and malignant melanoma (n = 32) were evaluated with a 22q12 dual-color, break-apart probe (Vysis, Downer's Grove, IL, USA), which spans the known common breakpoints in the EWS gene on chromosome 22 (introns 7-10). Signals from tumor cell nuclei were counted under a fluorescence microscope and the presence of red-green break-apart signals was recorded. Of the clear cell sarcoma cases, seven of 10 showed evidence of an EWS gene rearrangement with a mean of 81.6% positive cells per sample (range: 60-95%). All cases of malignant melanoma (n = 32) showed virtually absent break-apart signals in the EWS gene (less than 4% cells per case). FISH detects EWS gene rearrangement in a substantial proportion of clear cell sarcomas, with excellent specificity. Importantly, EWS FISH is negative in malignant melanoma, a clinically dissimilar tumor, which may closely mimic clear cell sarcoma histologically and immunohistochemically. As the studied probe can be utilized in routinely processed tissue, FISH provides an excellent alternative to reverse-transcriptase polymerase chain reaction in cases where fresh tissue is unavailable.

Diagnosis, Differential↗
PubMed2004

Suicide gene therapy of sarcoma cell lines using recombinant adeno-associated virus 2 vectors.

Soft-tissue sarcomas are mesenchymal tumors that respond poorly to systemic chemotherapy. Suicide gene therapy may be an alternative treatment strategy. Here we show a high susceptibility of human sarcoma cell lines for recombinant adeno-associated virus 2 (rAAV-2) suicide vectors: connective tissue sarcoma (HS-1), fibrosarcoma (HT-1080), Ewing sarcoma (RD-ES), Askin tumor (SK-N-MC), rhabdomyosarcoma (A-204) and soft-tissue sarcoma (WSKL-1). Several vectors containing the thymidine kinase (TK) gene under the control of either the cytomegalovirus promoter or the elongation-factor 1 alpha (EF1alpha) promoter were cloned and tested. Higher expression levels of the transgene were observed in the sarcoma lines when using the EF1alpha-suicide gene-containing vectors. A complete eradication of rAAV-2-EF1alpha-TK/eGFP (TK/enhanced green fluorescent protein fusion gene)-transduced tumor cells was shown following exposure to ganciclovir (2.5 microg/ml) in vitro, while at this dose level > 90% of mock-transduced tumor cells survived. Xenotransplantation tumor models (intraperitoneal, subcutaneous) for the human sarcoma cell line HS-1 were established in nonobese diabetic/severe-combined immunodeficient mice. Mice transplanted with rAAV-2-EF1alpha-TK/eGFP-transduced and ganciclovir-exposed tumor cells survived > 5 months while in the nontransduced group all mice had died approximately 1 month after inoculation. These data hold promise for further development of rAAV-2-based suicide gene therapy of sarcomas.

Animals↗
PubMed1999

Vascular endothelial growth factor-C (VEGF-C) and its receptors KDR and flt-4 are expressed in AIDS-associated Kaposi's sarcoma.

Kaposi's sarcoma is characterized by clusters of spindle-shaped cells that are considered to be tumor cells and by prominent vasculature. Whereas spindle cells are most likely endothelial in origin, it remains controversial whether they are of lymphatic or blood vascular derivation. To test the hypothesis that the lymphangiogenesis factor vascular endothelial growth factor-C and its receptors, KDR and flt-4, are involved in the pathogenesis of Kaposi's sarcoma, we performed in situ hybridizations and immunofluorescent stainings on human immunodeficiency virus-associated Kaposi's sarcoma. Spindle-shaped tumor cells strongly expressed KDR and flt-4 mRNA. Immunofluorescent staining confirmed expression of the flt-4 receptor in Kaposi's sarcoma cells, and double labeling revealed its colocalization with the endothelial cell marker CD31. Vascular endothelial growth factor-C was strongly expressed in blood vessels associated with Kaposi's sarcoma. In vitro, human dermal microvascular endothelial cells also expressed vascular endothelial growth factor-C mRNA that was further upregulated by vascular permeability factor/vascular endothelial growth factor. Vascular endothelial growth factor-C potently stimulated the proliferation of Kaposi's sarcoma tumor cells in vitro. These results demonstrate important paracrine functions of vascular endothelial growth factor-C, produced by blood vessels, in the pathogenesis of cutaneous Kaposi's sarcoma, and suggest a lymphatic origin and/or differentiation of Kaposi's sarcoma tumor cells.

Acquired Immunodeficiency Syndrome↗