Association of Epstein–Barr Virus with Leiomyosarcomas in Young People with AIDS

McClain, Kenneth L.; Leach, Charles T.; Jenson, Hal B.; Joshi, Vijay V.; Pollock, Brad H.; Parmley, Richard T.; DiCarlo, Frederick J.; Chadwick, Ellen G.; Murphy, Sharon B.

doi:10.1056/nejm199501053320103

Cited by 572 publications

(358 citation statements)

References 28 publications

(19 reference statements)

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“…Furthermore, some follicular dendritic cells were successfully infected with EBV in vitro (38). Recently, smooth muscle tumors in either immunosuppressed AIDS patients or recipients of liver transplant were found to be EBV infected (39,40).…”

Section: Discussionmentioning

confidence: 99%

Infection of human endothelial cells with Epstein-Barr virus.

Jones

Rivera

Sgadari

et al. 1995

The Journal of Experimental Medicine

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Interleukin-6 (IL-6) promotes growth and tumorigenicity of Epstein-Barr virus (EBV)-immortalized B cells, and is abnormally elevated in the serum of solid organ transplant recipients who develop EBV-positive posttransplant lymphoproliferative disease (PTLD), but not in control transplant recipients. Endothelial cells derived from PTLD lesions were found to secrete spontaneously high levels of IL-6 in vitro for up to 4 mo. We examined possible mechanisms for sustained IL-6 production by endothelial cells. Here, we show that EBV can infect endothelial cells in vitro. After 3-4 wk incubation with lethally irradiated EBV-positive, but not EBVnegative cell lines, a proportion of human umbilical cord-derived endothelial cells (HUVECs) expressed in situ the EBV-encoded small 1LNAs (EBER). Southern blot analysis after polymerase chain reaction showed EBV DNA in HUVEC that had been incubated with lethally irradiated EBV-positive ceils, but not in the controls. Exposure of HUVECs to lethally irradiated EBV-positive but not EBV-negative cell lines induced IL-6 production that was sustained for up to 120 d of culture. These studies identify endothelial cells as targets for EBV infection and raise the possibility that this infection may be important in the life cycle and pathology of EBV.

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Section: Discussionmentioning

confidence: 99%

Infection of human endothelial cells with Epstein-Barr virus.

Jones

Rivera

Sgadari

et al. 1995

The Journal of Experimental Medicine

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“…The smooth muscle tumors can occur in peripheral soft tissue, intracranial space, or visceral sites, and tumor multiplicity is common. [76][77][78][79][80][81][82][83][84][85] Molecular genetic analysis has shown that multiple tumor represent independent clones rather than dissemination of a single neoplastic clone. 85 In multiple tumor cases, tumors arising in the transplant are of donor cell origin, whereas those at the other sites arise from recipient cells, which also points to polyclonal origin of multiple tumors.…”

Section: Ebv-associated Smooth Muscle Tumorsmentioning

confidence: 99%

Smooth muscle tumors of soft tissue and non-uterine viscera: biology and prognosis

Miettinen

2014

Modern Pathology

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Smooth muscle tumors are here considered an essentially dichotomous group composed of benign leiomyomas and malignant leiomyosarcomas. Soft tissue smooth muscle tumors with both atypia and mitotic activity are generally diagnosed leiomyosarcomas acknowledging potential for metastasis. However, lesions exist that cannot be comfortably placed in either category, and in such cases the designation 'smooth muscle tumor of uncertain biologic potential' is appropriate. The use of this category is often necessary with limited sampling, such as needle core biopsies. Benign smooth muscle tumors include smooth muscle hamartoma and angioleiomyoma. A specific category of leiomyomas are estrogen-receptor positive ones in women. These are similar to uterine leiomyomas and can occur anywhere in the abdomen and abdominal wall. Leiomyosarcomas can occur at any site, although are more frequent in the retroperitoneum and proximal extremities. They are recognized by likeness to smooth muscle cells but can undergo pleomorphic evolution ('dedifferentiation'). Presence of smooth muscle actin is nearly uniform and desmin-positivity usual. This and the lack of KIT expression separate leiomyosarcoma from GIST, an important problem in abdominal soft tissues. EBVassociated smooth muscle tumors are a specific subcategory occurring in AIDS or post-transplant patients. These tumors can have incomplete smooth muscle differentiation but show nuclear EBER as a diagnostic feature. In contrast to many other soft tissue tumors, genetics of smooth muscle tumors are poorly understood and such diagnostic testing is not yet generally applicable in this histogenetic group. Leiomyosarcomas are known to be genetically complex, often showing 'chaotic' karyotypes including aneuploidy or polyploidy, and no recurrent tumor-specific translocations have been detected.

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“…1 EBV infection and consistent presence of EBV genome are associated with numerous malignant diseases, including African Burkitt lymphomas, 2 Hodgkin disease, 3 nasopharyngeal carcinoma (NPC), 4,5 leiomyosarcomas, 6 AIDS-associated central nervous system lymphomas, 7 T-cell lymphomas, 8 some gastric carcinomas, 9,10 breast cancers, 11 liver cancers, 12 lung cancers, colon cancers and prostate cancers. 13 In addition, post-transplant lymphoproliferative disorder (PTLD), one of the most dreaded complications in immunosuppressed organ allograft recipients is also a frequent problem due to EBV infection.…”

Section: Introductionmentioning

confidence: 99%

Regulation of cellular and viral protein expression by the Epstein-Barr virus transcriptional regulator Zta: Implications for therapy of EBV associated tumors

Chen¹,

Li²,

Guo³

2009

Cancer Biology & Therapy

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Association of Epstein–Barr Virus with Leiomyosarcomas in Young People with AIDS

Abstract: EBV can infect smooth-muscle cells, at least in patients with AIDS, and it may contribute to the pathogenesis of leiomyomas and leiomyosarcomas in children with AIDS. EBV seems to play no part in smooth-muscle tumors in HIV-negative children.

Cited by 572 publications

References 28 publications

Infection of human endothelial cells with Epstein-Barr virus.

Infection of human endothelial cells with Epstein-Barr virus.

Smooth muscle tumors of soft tissue and non-uterine viscera: biology and prognosis

Regulation of cellular and viral protein expression by the Epstein-Barr virus transcriptional regulator Zta: Implications for therapy of EBV associated tumors

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