The Biology of Kaposi’s Sarcoma

  • Brian Herndier
  • Don Ganem
Part of the Cancer Treatment and Research book series (CTAR, volume 104)

Abstract

The idea that KS might have an infectious cause is an old one that derives from several sources. First, the complex histology of the lesion, its multicentric nature, the indolent character of the disease (in its classical form), its occasional spontaneous regression and the evidence for oligo-or poly-clonality (see below) all suggest that KS is not a traditional malignancy. As early as the 1970’s speculation abounded that the African form was linked to cytomegalovirus (CMV) infection1-3a notion that was ultimately disproven. Suspicions of a viral etiology were again aroused in the AIDS era, since HIV-positive subjects appeared to be at enormous risk for developing this once-rare condition4. Although it was natural to wonder whether HIV itself might be the proximate cause of KS, this notion was complicated by the finding that KS spindle cells do not harbor HIV DNA. This led to suggestions that HIV-infected cells might provide factors in trans that stimulate KS spindle cells to grow, a notion for which there is considerable in vitro evidence (see below). But epidemiological studies of AIDS-KS in the US and Europe soon established the decisive fact that even among HIV-positive subjects there were wide differences in KS risk4. Male homosexuals with HIV are 20-30 times more likely to develop KS than HIV-infected hemophiliacs or IV drug users and KS is rarer still in children with vertically-acquired HIV. These seminal observations suggested that a second, possibly sexually transmitted, factor was a critical determinant of KS risk and precipitated a search for potential pathogens in KS tissue.

Keywords

Europe Codon Tyrosine Leukemia Pneumonia 

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References

  1. 1.
    Giraldo G, Beth E, Kourilsky FM, et al. Antibody patterns to herpesviruses in kaposi’s sarcoma: serological association of european kaposi’s sarcoma with cytomegalovirus. hit J Cancer l5(5):839–48, 1975.Google Scholar
  2. 2.
    Giraldo G, Beth E, Kyalwazi SK. Etiological implications on Kaposi’s sarcoma. Antibiot Chemother 29:12–31, 1981.PubMedGoogle Scholar
  3. 3.
    Glaser R, Geder L, StJeor S, Michelson-Fiske S, Haguenau F. Partial characterization of a herpes-type virus (K9V) derived from Kaposi’s sarcoma. J Natl Cancer Inst 59(1):55–60, 1977.PubMedGoogle Scholar
  4. 4.
    Beral V, Peterman TA, Berkelman RL, Jaffe HW. Kaposi’s sarcoma among persons with AIDS: a sexually transmitted infection? [see comments]. Lancet 335(8682):123–8, 1990.PubMedCrossRefGoogle Scholar
  5. 5.
    Chang Y, Cesarman E, Pessin MS, et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma [see comments] Science 266(5192):1865–9, 1994.PubMedCrossRefGoogle Scholar
  6. 6.
    Lisitsyn N, Lisitsyn N, Wigler M. Cloning the difference between two genomes. Science 259:946–959, 1993.PubMedCrossRefGoogle Scholar
  7. 7.
    Moore PS, Chang Y. Detection of herpesvirus-like DNA sequences in Kaposi’s sarcoma in patients with and without HIV infection [see comments]. N Engl J Med 332(18):1181–5, 1995.PubMedCrossRefGoogle Scholar
  8. 8.
    Russo JJ, Bohenzky RA, Chien MC, et al. Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). Proc Natl Acad Sci U S A 93(25):14862–7, 1996.PubMedCrossRefGoogle Scholar
  9. 9.
    Cesarman E, Chang Y, Moore PS, Said JW, Knowles DM. Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in AIDS- related body-cavity-based lymphomas [see comments]. N Engl J Med 332(18):1186–91, 1995.PubMedCrossRefGoogle Scholar
  10. 10.
    Komanduri KV, Luce JA, McGrath MS, Herndier BG, Ng VL. The natural history and molecular heterogeneity of HIV-associated primary malignant lymphomatous effusions. J Acquir Immune Defic Syndr Hum Retrovirol 13(3):215–26, 1996.PubMedCrossRefGoogle Scholar
  11. 11.
    Zhong W, Wang H, Herndier B, Ganem D. Restricted expression of Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genes in Kaposi sarcoma. Proc Natl Acad Sci U S A 93(13):6641–6, 1996.PubMedCrossRefGoogle Scholar
  12. 12.
    Neipel F, Albrecht JC, Fleckenstein B. Cell-homologous genes in the Kaposi’s sarcoma-associated rhadinovirus human herpesvirus 8: determinants of its pathogenicity? J Virol 71(6):4187–92, 1997.PubMedGoogle Scholar
  13. 13.
    Lagunoff M, Ganem D. The structure and coding organization of the genomic termini of Kaposi’s sarcoma-associated herpesvirus. Virology 236(1):147–54, 1997.PubMedCrossRefGoogle Scholar
  14. 14.
    Renne R, Lagunoff M, Zhong W, Ganem D. The size and conformation of Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) DNA in infected cells and virions. J Virol 70(11):8151–4, 1996.PubMedGoogle Scholar
  15. 15.
    Rainbow L, Platt GM, Simpson GR, et al. The 222- to 234-kilodalton latent nuclear protein (LNA) of Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) is encoded by orf73 and is a component of the latency-associated nuclear antigen. J Virol 71(8):5915–21, 1997.PubMedGoogle Scholar
  16. 16.
    Dittmer D, Lagunoff M, Renne R, Staskus K, Haase A, Ganem D. A cluster of latently expressed genes in Kaposi’s sarcoma-associated herpesvirus. J Virol 72(10):8309–15, 1998.PubMedGoogle Scholar
  17. 17.
    Kedes DH, Lagunoff M, Renne R, Ganem D Identification of the gene encoding the major Iatency-associated nuclear antigen of the Kaposi’s sarcoma-associated herpesvirus. J Clin Invest 100(10):2606–10, 1997.PubMedCrossRefGoogle Scholar
  18. 18.
    Ballestas ME, Chatis PA, Kaye KM. Efficient persistence of extrachromosomal KSHV DNA mediated by latency-associated nuclear antigen. Science 284(5414):641–4, 1999.PubMedCrossRefGoogle Scholar
  19. 19.
    Chang Y, Moore PS, Talbot SJ, et al. Cyclin encoded by KS herpesvirus [letter]. Nature 382(6590):410, 1996.PubMedCrossRefGoogle Scholar
  20. 20.
    Li M, Lee H, Yoon DW, et al. Kaposi’s sarcoma-associated herpesvirus encodes a functional cyclin. J Virol 71(3):1984–91, 1997.PubMedGoogle Scholar
  21. 21.
    Godden-Kent D, Talbot SJ, Boshoff C, et al. The cyclin encoded by Kaposi’s sarcoma-associated herpesvirus stimulates cdk6 to phosphorylate the retinoblastoma protein and histone H1. J Virol 71(6):4193–8, 1997.PubMedGoogle Scholar
  22. 22.
    Thome M, Schneider P, Hofmann K, et al. Viral FLICE-inhibitory proteins (FLIPS) prevent apoptosis induced by death receptors. Nature 386(6624):517–21, 1997.PubMedCrossRefGoogle Scholar
  23. 23.
    Djerbi M, Screpanti V, Catrina AI, Bogen B, Biberfeld P, Grandien A. The inhibitor of death receptor signaling, FLICE-inhibitory protein defines a new class of tumor progression factors [see comments]. J Exp Med 190(7):1025–32, 1999.PubMedCrossRefGoogle Scholar
  24. 24.
    Arvanitakis L, Geras-Raaka E, Varna A, Gershengorn MC, Cesarman E. Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation [see comments]. Nature 385(6614):347–50, 1997.PubMedCrossRefGoogle Scholar
  25. 25.
    Sand R, Sato T, Bohenzky RA, Russo JJ, Chang Y. Kaposi’s sarcoma-associated herpesvirus encodes a functional bcl-2 homologue. Nat Med 3(3):293–8, 1997.CrossRefGoogle Scholar
  26. 26.
    Staskus KA, Zhong W, Gebhard K, et al. Kaposi’s sarcoma-associated herpesvirus gene expression in endothelial (spindle) tumor cells. J Virol 71(1):715–9, 1997.PubMedGoogle Scholar
  27. 27.
    Ensoli B, Sturzl M. Kaposi’s sarcoma: a result of the interplay among inflammatory cytokines, angiogenic factors and viral agents. Cytokine Growth Factor Rev 9(1):63–83, 1998.PubMedCrossRefGoogle Scholar
  28. 28.
    Ensoli B, Barillari G, Gallo RC. Cytokines and growth factors in the pathogenesis of AIDS-associated Kaposi’s sarcoma. Immunol Rev 127:147–55, 1992.PubMedCrossRefGoogle Scholar
  29. 29.
    Offermann MK. HHV-8: a new herpesvirus associated with Kaposi’s sarcoma. Trends Microbiol 4(10):383–6, 1996.PubMedCrossRefGoogle Scholar
  30. 30.
    Neipel F, Albrecht JC, Ensser A, et al. Human herpesvirus 8 encodes a homolog of interleukin-6. J Virol 71(1):839–42, 1997.PubMedGoogle Scholar
  31. 31.
    Molden J, Chang Y, You Y, Moore PS, Goldsmith MA. A Kaposi’s sarcoma-associated herpesvirus-encoded cytokine homolog (vIL- 6) activates signaling through the shared gp130 receptor subunit. J Biol Chem 272(31):19625–31, 1997.PubMedCrossRefGoogle Scholar
  32. 32.
    Moore PS, Boshoff C, Weiss RA, Chang Y. Molecular mimicry of human cytokine and cytokine response pathway genes by KSHV. Science 274(5293):1739–44, 1996.PubMedCrossRefGoogle Scholar
  33. 33.
    Gao SJ, Boshoff C, Jayachandra S, Weiss RA, Chang Y, Moore PS. KSHV ORF K9 (vIRF) is an oncogene which inhibits the interferon signaling pathway. Oncogene 15(16):1979–85, 1997.PubMedCrossRefGoogle Scholar
  34. 34.
    Li M, Lee H, Guo J, et al. Kaposi’s sarcoma-associated herpesvirus viral interferon regulatory factor. J Virol 72(7):5433–40, 1998.PubMedGoogle Scholar
  35. 35.
    Zimring JC, Goodbourn S, Offermann MK. Human herpesvirus 8 encodes an interferon regulatory factor (IRF) homolog that represses IRF-1-mediated transcription. J Virol 72(1):701–7, 1998.PubMedGoogle Scholar
  36. 36.
    Lee H, Veazey R, Williams K, et al. Deregulation of cell growth by the Kl gene of Kaposi’s sarcoma-associated herpesvirus. Nat Med 4(4):435–40, 1998.PubMedCrossRefGoogle Scholar
  37. 37.
    Lee H, Guo J, Li M, et al. Identification of an immunoreceptor tyrosine-based activation motif of K1 transforming protein of Kaposi’s sarcoma-associated herpesvirus. Mol Cell Biol 18(9):5219–28, 1998.PubMedGoogle Scholar
  38. 38.
    Lagunoff M, Majeti R, Weiss A, Ganem D. Deregulated signal transduction by the K1 gene product of Kaposi’s sarcoma-associated herpesvirus. Proc Natl Acad Sci U S A 96(10):5704–9, 1999.PubMedCrossRefGoogle Scholar
  39. 39.
    Schulz T. Kaposi’s sarcoma-associated herpesvirus (human herpesvirus-8). J Gen Virol 79:1573–1591, 1998.PubMedGoogle Scholar
  40. 40.
    Kedes D, Operskalski E, Busch M, Kohn R, Flood J, Ganem D. The seroepidemiology of human herpesvirus 8 (Kaposi’s sarcoma-associated herpesvirus): distribution of infection in KS risk groups and evidence for sexual transmission. Nature Med.2(918–924), 1996.PubMedCrossRefGoogle Scholar
  41. 41.
    Kedes DH, Ganem D, Ameli N, Bacchetti P, Greenblatt R. The prevalence of serum antibody to human herpesvirus 8 (Kaposi sarcoma-associated herpesvirus) among HIVseropositive and high-risk HIV- seronegative women. Jama 277(6):478–81, 1997.PubMedCrossRefGoogle Scholar
  42. 42.
    Gao SJ, Kingsley L, Li M, et al. KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi’s sarcoma [see comments]. Nat Med 2(8):925–8, 1996.PubMedCrossRefGoogle Scholar
  43. 43.
    Simpson GR, Schulz TF, Whitby D, et al. Prevalence of Kaposi’s sarcoma associated herpesvirus infection measured by antibodies to recombinant capsid protein and latent immunofluorescence antigen [see comments]. Lancet 348(9035):1133–8, 1996.PubMedCrossRefGoogle Scholar
  44. 44.
    Chandran B, Smith MS, Koelle DM, Corey L, Horvat R, Goldstein E. Reactivities of human sera with human herpesvirus-8-infected BCBL-1 cells and identification of HHV-8specific proteins and glycoproteins and the encoding cDNAs. Virology 243(1):208–17, 1998.PubMedCrossRefGoogle Scholar
  45. 45.
    Whitby D, Howard MR, Tenant-Flowers M, et al. Detection of Kaposi sarcoma associated herpesvirus in peripheral blood of HIV-infected individuals and progression to Kaposi’s sarcoma [see comments]. Lancet 346(8978):799–802, 1995.PubMedCrossRefGoogle Scholar
  46. 46.
    Whitby D, Luppi M, Barozzi P, Boshoff C, Weiss RA, Torelli G. Human herpesvirus 8 seroprevalence in blood donors and lymphoma patients from different regions of Italy [see comments]. J Natl Cancer Inst 90(5):395–7, 1998.PubMedCrossRefGoogle Scholar
  47. 47.
    Calabro ML, Sheldon J, Favero A, et al. Seroprevalence of Kaposi’s sarcoma-associated herpesvirus/human herpesvirus 8 in several regions of Italy. J Hum Virol 1(3):207–13, 1998.PubMedGoogle Scholar
  48. 48.
    Sitas F, Carrara H, Beral V, et al. Antibodies against human herpesvirus 8 in black South African patients with cancer [see comments]. N Engl J Med 340(24):1863–71, 1999.PubMedCrossRefGoogle Scholar
  49. 49.
    Gessain A, Mauclere P, van Beveren M, et al. Human herpesvirus 8 primary infection occurs during childhood in Cameroon, Central Africa. Int J Cancer 81(2):189–92, 1999.PubMedCrossRefGoogle Scholar
  50. 50.
    Moore PS, Kinglsley LA, Holmberg SD, et al. Kaposi’s sarcoma-associated herpesvirus infection prior to onset of Kaposi’s sarcoma. AIDS 10:175–180, 1995.CrossRefGoogle Scholar
  51. 51.
    Martin JN, Ganem DE, Osmond DH, Page-Shafer KA, Macrae D, Kedes DH. Sexual transmission and the natural history of human herpesvirus 8 infection. N Engl J Med 338(14):948–54, 1998.PubMedCrossRefGoogle Scholar
  52. 52.
    Martin DF, Kuppermann BD, Wolitz RA, Palestine AG, Li H, Robinson CA. Oral ganciclovir for patients with cytomegalovirus retinitis treated with a ganciclovir implant. Roche Ganciclovir Study Group. N. Engl. J. Med. 340:1063–1070, 1999.PubMedCrossRefGoogle Scholar
  53. 53.
    Kedes DH, Operskalski E, Busch M, Kohn R, Flood J, Ganem D. The seroepidemiology of human herpesvirus 8 (Kaposi’s sarcoma-associated herpesvirus): distribution of infection in KS risk groups and evidence for sexual transmission [see comments] [published erratum appears in Nat Med Sep;2(9):1041]. Nat Med 1996;2(8):918–24, 1996.CrossRefGoogle Scholar
  54. 54.
    Blauvelt A, Sei S, Cook PM, Schulz TF, Jeang KT. Human herpesvirus 8 infection occurs following adolescence in the United States. J Infect Dis 176(3):771–4, 1997.PubMedCrossRefGoogle Scholar
  55. 55.
    Goedert JJ, Kedes DH, Ganem D. Antibodies to human herpesvirus 8 in women and infants born in Haiti and the USA [letter]. Lancet 349(9062):1368, 1997.PubMedCrossRefGoogle Scholar
  56. 56.
    Koelle DM, Huang ML, Chandran B, Vieira J, Piepkorn M, Corey L. Frequent detection of Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) DNA in saliva of human immunodeficiency virus-infected men: clinical and immunologic correlates. J Infect Dis 176(1):94–102, 1997.PubMedCrossRefGoogle Scholar
  57. 57.
    Vieira J, Huang ML, Koelle DM, Corey L. Transmissible Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) in saliva of men with a history of Kaposi’s sarcoma. J Virol 71(9):7083–7, 1997.PubMedGoogle Scholar
  58. 58.
    Tacchetti C, Favre A, Moresco L, et al. HIV is trapped and masked in the cytoplasm of lymph node follicular dendritic cells [see comments]. Am J Pathol 150(2):533–42, 1997.PubMedGoogle Scholar
  59. 59.
    Tasaka T, Said JW, Koeffler HP. Absence of HHV-8 in Prostate and Semen (letter to the editor). N Engl J Med 335(16):1237–1238, 1996.PubMedCrossRefGoogle Scholar
  60. 60.
    Tasaka T, Said JW, Morosetti R, et al. Is Kaposi’s sarcoma--associated herpesvirus ubiquitous in urogenital and prostate tissues? Blood 89(5):1686–9, 1997.PubMedGoogle Scholar
  61. 61.
    Mayama S, Cuevas LE, Sheldon J, et al. Prevalence and transmission of Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) in Ugandan children and adolescents. Int J Cancer 77(6):817–20, 1998.PubMedCrossRefGoogle Scholar
  62. 62.
    Rettig MB, Ma HJ, Vescio RA, et al. Kaposi’s sarcoma-associated herpesvirus infection of bone marrow dendritic cells from multiple myeloma patients [see comments]. Science 276(5320):1851–4, 1997.PubMedCrossRefGoogle Scholar
  63. 63.
    Said JW, Rettig MR, Heppner K, et al. Localization of Kaposi’s sarcoma-associated herpesvirus in bone marrow biopsy samples from patients with multiple myeloma [see comments]. Blood 90(11):4278–82, 1997.PubMedGoogle Scholar
  64. 64.
    Gaidano G, Castanos-Velez E, Biberfeld P. Lymphoid disorders associated with HHV8/KSHV infection: facts and contentions. Med Oncol 16(1):8–12, 1999.PubMedCrossRefGoogle Scholar
  65. 65.
    Cohen SS, Weinstein MD, Herndier BG, Anhalt GJ, Blauvelt A. No evidence of human herpesvirus 8 infection in patients with paraneoplastic pemphigus, pemphigus vulgaris, or pemphigus foliaceus. J Invest Dermatol 111(5):781–3, 1998.PubMedCrossRefGoogle Scholar
  66. 66.
    Bellos F, Goldschmidt H, Dorner M, Ho AD, Moos M. Bone marrow derived dendritic cells from patients with multiple myeloma cultured with three distinct protocols do not bear Kaposi’s sarcoma associated herpesvirus DNA. Ann Oncol 10(3):323–7, 1999.PubMedCrossRefGoogle Scholar
  67. 67.
    Cesarman E, Knowles DM. The role of Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8) in lymphoproliferative diseases. Semin Cancer Biol 9(3):165–74, 1999.PubMedCrossRefGoogle Scholar
  68. 68.
    Dupin N, Fisher C, Kellam P, et al. Distribution of human herpesvirus-8 latently infected cells in Kaposi’s sarcoma, multicentric Castleman’s disease, and primary effusion lymphoma. Proc Natl Acad Sci U S A 96(8):4546–51, 1999.PubMedCrossRefGoogle Scholar
  69. 69.
    Olsen SJ, Tarte K, Sherman W, et al. Evidence against KSHV infection in the pathogenesis of multiple myeloma. Virus Res 57(2):197–202, 1998.PubMedCrossRefGoogle Scholar
  70. 70.
    Raje N, Gong J, Chauhan D, et al. Bone marrow and peripheral blood dendritic cells from patients with multiple myeloma are phenotypically and functionally normal despite the detection of Kaposi’s sarcoma herpesvirus gene sequences. Blood 93(5):1487–95, 1999.PubMedGoogle Scholar
  71. 71.
    Yi Q, Ekman M, Anton D, et al. Blood dendritic cells from myeloma patients are not infected with Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8). Blood 92(2):402–4, 1998.Google Scholar
  72. 72.
    Poole LJ, Zong JC, Ciufo DM, et al. Comparison of genetic variability at multiple loci across the genomes of the major subtypes of Kaposi’s sarcoma-associated herpesvirus reveals evidence for recombination and for two distinct types of open reading frame K15 alleles at the right-hand end. J Virol 73(8):6646–60, 1999.PubMedGoogle Scholar
  73. 73.
    Hayward GS. KSHV strains: the origins and global spread of the virus. Semin Cancer Biol 9(3):187–99, 1999.PubMedCrossRefGoogle Scholar
  74. 74.
    Zong JC, Metroka C, Reitz MS, Nicholas J, Hayward GS. Strain variability among Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genomes: evidence that a large cohort of United States AIDS patients may have been infected by a single common isolate [see comments]. J Virol 71(3):2505–11, 1997.PubMedGoogle Scholar
  75. 75.
    Sarid R, Wiezorek JS, Moore PS, Chang Y. Characterization and cell cycle regulation of the major Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) latent genes and their promoter. J Virol 73(2):1438–46, 1999.PubMedGoogle Scholar
  76. 76.
    Grundhoff X, Ganem D. unpublished results..Google Scholar
  77. 77.
    Mann DJ, Child ES, Swanton C, Laman H, Jones N. Modulation of p27(Kipl) levels by the cyclin encoded by Kaposi’s sarcoma-associated herpesvirus. Embo J 18(3):654–63, 1999.PubMedCrossRefGoogle Scholar
  78. 78.
    Swanton C, Mann DJ, Fleckenstein B, Neipel F, Peters G, Jones N. Herpes viral cyclin/Cdk6 complexes evade inhibition by CDK inhibitor proteins. Nature 390(6656):184–7, 1997.PubMedCrossRefGoogle Scholar
  79. 79.
    Sadler R, Wu L, Forghani B, et al. A complex translational program generates multiple novel proteins from the latently expressed kaposin (K12) locus of Kaposi’s sarcoma-associated herpesvirus. J Virol 73(7):5722–30, 1999.PubMedGoogle Scholar
  80. 80.
    Sadler R, Ganem D. unpublished observations..Google Scholar
  81. 81.
    Glenn M, Rainbow L, Aurad F, Davison A, Schulz TF. Identification of a spliced gene from Kaposi’s sarcoma-associated herpesvirus encoding a protein with similarities to latent membrane proteins 1 and 2A of Epstein-Barr virus. J Virol 73(8):6953–63, 1999.PubMedGoogle Scholar
  82. 82.
    Choi JK, Lee BS, Shim SN, Li M, Jung JU. Identification of the novel K15 gene at the rightmost end of the Kaposi’s sarcoma-associated herpesvirus genome. J Virol 74(1):436–46,2000.PubMedCrossRefGoogle Scholar
  83. 83.
    Flore O, Rafii S, Ely S, O’Leary JJ, Hyjek EM, Cesarman E. Transformation of primary human endothelial cells by Kaposi’s sarcoma-associated herpesvirus. Nature 394(6693):588–92, 1998.PubMedCrossRefGoogle Scholar
  84. 84.
    Boshoff C, Endo Y, Collins PD, et al. Angiogenic and HIV-inhibitory functions of KSHV-encoded chemokines [see comments]. Science 278(5336):290–4, 1997.PubMedCrossRefGoogle Scholar
  85. 85.
    Boshoff C. Coupling herpesvirus to angiogenesis. Nature 391:24–25, 1998.PubMedCrossRefGoogle Scholar
  86. 86.
    Bais C, Santomasso B, Coso O, et al. G-protein-coupled receptor of Kaposi’s sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator [see comments] [published erratum appears in Nature 1998 Mar 12;392(6672):210]. Nature 391(6662):86–9, 1998.PubMedCrossRefGoogle Scholar
  87. 87.
    Lee H, Guo J, Li M, et al. Identification of an Immunoreceptor Tyrosine-Based Activation Motif of K1 transforming Protein of Kaposi’s Sarcoma-associated Herpesvirus. Mol. Cell Biol. 18(9):5219–5228, 1998.Google Scholar
  88. 88.
    Lagunoff M, Ganem D. unpublished observations.Google Scholar
  89. 89.
    Desrosiers RC, Sasseville VG, Czajak SC, et al. A herpesvirus of rhesus monkeys related to the human Kaposi’s sarcoma-associated herpesvirus. J Virol 71(12):9764–9, 1997.PubMedGoogle Scholar
  90. 90.
    Searles RP, Bergquam EP, Axthelm MK, Wong SW. Sequence and genomic analysis of a Rhesus macaque rhadinovirus with similarity to Kaposi’s sarcoma-associated herpesvirus/human herpesvirus 8. J Virol 73(4):3040–53, 1999.PubMedGoogle Scholar
  91. 91.
    Kaleeba JA, Bergquam EP, Wong SW. A rhesus macaque rhadinovirus related to Kaposi’s sarcoma-associated herpesvirus/human herpesvirus 8 encodes a functional homologue of interleukin-6. J Virol 73(7):6177–81, 1999.PubMedGoogle Scholar
  92. 92.
    Sternbach G, Varon J. Moritz Kaposi: idiopathic pigmented sarcoma of the skin J Emerg Med 13(5):671–4, 1995.PubMedCrossRefGoogle Scholar
  93. 93.
    Parravicini C, Olsen SJ, Capra M, et al. Risk of Kaposi’s sarcoma-associated herpes virus transmission from donor allografts among Italian posttransplant Kaposi’s sarcoma patients. Blood 90(7):2826–9, 1997.PubMedGoogle Scholar
  94. 94.
    Nocera A, Corbellino M, Valente U, et al. Posttransplant human herpes virus 8 infection and seroconversion in a Kaposi’s sarcoma affected kidney recipient transplanted from a human herpes virus 8 positive living related donor. Transplant Proc 30(5):2095–6, 1998.PubMedCrossRefGoogle Scholar
  95. 95.
    Regamey N, Tamm M, Binet I, Thiel G, Erb P, Cathomas G. Transplantation-associated Kaposi’s sarcoma: herpesvirus 8 transmission through renal allografts. Transplant Proc 31(1–2):922–3, 1999.PubMedCrossRefGoogle Scholar
  96. 96.
    Gottlieb MS, Schroff R, Schanker HM, et al. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N Engl J Med 305(24):1425–31, 1981.PubMedCrossRefGoogle Scholar
  97. 97.
    Friedman-Kien AE, Laubenstein LJ, Rubinstein P, et al. Disseminated Kaposi’s sarcoma in homosexual men. Ann Intern Med 96(6 Pt 1):693–700, 1982.PubMedGoogle Scholar
  98. 98.
    LeBoit PE. Dermatopathologic findings in patients infected with HIV. Dermatol Clin 10(1):59–71, 1992.PubMedGoogle Scholar
  99. 99.
    Cockerell CJ. Histopathological features of Kaposi’s sarcoma in HIV infected individuals. Cancer Sury 10:73–89, 1991.Google Scholar
  100. 100.
    Cockerell CJ. Organ-specific manifestations of HIV infection. II. Update on cutaneous manifestations of HIV infection. Aids 7(Suppl 1):S213–8, 1993.PubMedCrossRefGoogle Scholar
  101. 101.
    Myrie C, Hapke M, Ackerman AB. Capsule dermatopathology. Kaposi’s sarcoma vs. pyogenic granuloma. J Dermatol Surg 2(2):116–7, 1976.PubMedGoogle Scholar
  102. 102.
    Ackerman AB. Subtle clues to diagnosis by conventional microscopy. The patch stage of Kaposi’s sarcoma. Am J Dermatopathol 1(2):165–72, 1979.PubMedCrossRefGoogle Scholar
  103. 103.
    Gottlieb GJ, Ackerman AB. Kaposi’s sarcoma: an extensively disseminated form in young homosexual men. Hum Pathol 13(10):882–92, 1982.PubMedCrossRefGoogle Scholar
  104. 104.
    Dorfman RF. The histogenesis of Kaposi’s sarcoma. Lymphology 17(3):76–7, 1984.PubMedGoogle Scholar
  105. 105.
    Dorfman RF. Cutaneous and lymphadenopathic Kaposi’s sarcoma in Africa and the USA with observations on persistent lymphadenopathy in homosexual men at risk for the acquired immunodeficiency syndrome. Front Radiat Ther Oncol 19:105–16, 1985.PubMedGoogle Scholar
  106. 106.
    Dorfman RF. Kaposi’s sarcoma: evidence supporting its origin from the lymphatic system. Lymphology 21(1):45–52, 1988.PubMedGoogle Scholar
  107. 107.
    Orenstein JM, Alkan S, Blauvelt A, et al. Visualization of human herpesvirus type 8 in Kaposi’s sarcoma by light and transmission electron microscopy. Aids 11(5):F35–45, 1997.PubMedCrossRefGoogle Scholar
  108. 108.
    Monini P, Colombini S, Sturzl M, et al. Reactivation and persistence of human herpesvirus-8 infection in B cells and monocytes by Th-1 cytokines increased in Kaposi’s sarcoma [see comments]. Blood 93(12):4044–58, 1999.PubMedGoogle Scholar
  109. 109.
    Wade TR, Kamino H, Ackerman AB. A histologic atlas of vascular lesions. J Dermatol Surg Oncol 4(11):845–50, 1978.PubMedGoogle Scholar
  110. 110.
    Aoki Y, Jaffe ES, Chang Y, et al. Angiogenesis and hematopoiesis induced by Kaposi’s sarcoma-associated herpesvirus-encoded interleukin-6 [see comments]. Blood 93(12):4034–43, 1999.PubMedGoogle Scholar
  111. 111.
    Parravinci C, Corbellino M, Paulli M, et al. Expression of a virus-derived cytokine, KSHV vIL-6, in HIV-seronegative Castleman’s disease. Am J Pathol 151(6):1517–22, 1997.Google Scholar
  112. 112.
    Staskus KA, Sun R, Miller G, et al. Cellular tropism and viral interleukin-6 expression distinguish human herpesvirus 8 involvement in Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. J Virol 73(5):4181–7, 1999.PubMedGoogle Scholar
  113. 113.
    Atagi S, Sakatani M, Akira M, Yamamoto S, Ueda E. Pulmonary hyalinizing granuloma with Castleman’s disease. Intern Med 33(11):689–91, 1994.PubMedCrossRefGoogle Scholar
  114. 114.
    Mandel C, Silberstein M, Hennessy O. Case report: fatal pulmonary Kaposi’s sarcoma and Castleman’s disease in a renal transplant recipient. Br J Radiol 66(783):264–5, 1993.PubMedCrossRefGoogle Scholar
  115. 115.
    Parravicini C, Chandran B, Corbellino M, Berti M, Moore P, Chang Y. Differential viral protein expression in KSHV-associated diseases: Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. Blood 1999.Google Scholar
  116. 116.
    Amazon K, Rywlin AM. Subtle clues to diagnosis by conventional microscopy. Lymph node involvement in Kaposi’s sarcoma. Am J Dermatopathol 1(2):173–6, 1979.PubMedCrossRefGoogle Scholar
  117. 117.
    Ruszczak Z, Mayer da Silva A, Orfanos CE. Angioproliferative changes in clinically noninvolved, perilesional skin in AIDS-associated Kaposi’s sarcoma. Dermatologica 175(6):270–9, 1987.PubMedCrossRefGoogle Scholar
  118. 118.
    Ruszczak Z, Mayer-Da Silva A, Orfanos CE. Kaposi’s sarcoma in AIDS. Multicentric angioneoplasia in early skin lesions. Am J Dermatopathol 9(5):388–98, 1987.PubMedCrossRefGoogle Scholar
  119. 119.
    Ambroziak JA, Blackbourn DJ, Herndier BG, et al. Herpes-like sequences in HIV-infected and uninfected Kaposi’s sarcoma patients [letter; comment]. Science 268(5210):582–3, 1995.PubMedCrossRefGoogle Scholar
  120. 120.
    Orenstein JM, Herndier B. Appearance of human herpesvirus 8 on electron microscopy [letter; comment]. N Engl J Med 340(1):62–4, 1999.PubMedGoogle Scholar
  121. 121.
    Boshoff C, Schulz TF, Kennedy MM, et al. Kaposi’s sarcoma-associated herpesvirus infects endothelial and spindle cells. Nat Med 1(12):1274–8, 1995.PubMedCrossRefGoogle Scholar
  122. 122.
    Blasig C, Zietz C, Haar B, et al. Monocytes in Kaposi’s sarcoma lesions are productively infected by human herpesvirus 8. J Virol 71(10):7963–8, 1997.PubMedGoogle Scholar
  123. 123.
    McGrath MS, Shiramizu BT, Herndier BG. Identification of a clonal form of HIV in early Kaposi’s sarcoma: evidence for a novel model of oncogenesis, “sequential neoplasia”. J Acquir Immune Defic Syndr Hum Retrovirol 8(4):379–85, 1995.PubMedCrossRefGoogle Scholar
  124. 124.
    Sastry KJ, Reddy HR, Pandita R, Totpal K, Aggarwal BB. HIV-1 tat gene induces tumor necrosis factor-beta (lymphotoxin) in a human B-lymphoblastoid cell line. J Biol Chem 265(33):20091–3, 1990.PubMedGoogle Scholar
  125. 125.
    Ensoli B, Barillari G, Gallo RC. Pathogenesis of AIDS-associated Kaposi’s sarcoma. Hematol Oncol Clin North Am 5(2):281–95, 1991.PubMedGoogle Scholar
  126. 126.
    Ensoli B, Salahuddin SZ, Gallo RC. AIDS-associated Kaposi’s sarcoma: a molecular model for its pathogenesis. Cancer Cells 1(3):93–6, 1989.PubMedGoogle Scholar
  127. 127.
    Buonaguro L, Barillari G, Chang HK, et al. Effects of the human immunodeficiency virus type 1 Tat protein on the expression of inflammatory cytokines. J Virol 66(12):7159–67, 1992.PubMedGoogle Scholar
  128. 128.
    Ensoli B, Barillari G, Salahuddin SZ, Gallo RC, Wong-Staal F. Tat protein of HIV-1 stimulates growth of cells derived from Kaposi’s sarcoma lesions of AIDS patients. Nature 345(6270):84–6, 1990.PubMedCrossRefGoogle Scholar
  129. 129.
    Ensoli B, Nakamura S, Salahuddin SZ, et al. AIDS-Kaposi’s sarcoma-derived cells express cytokines with autocrine and paracrine growth effects. Science 243(4888):223–6, 1989.PubMedCrossRefGoogle Scholar
  130. 130.
    Albini A, Barillari G, Benelli R, Gallo RC, Ensoli B. Angiogenic properties of human immunodeficiency virus type 1 Tat protein. Proc Nail Acad Sci U S A 92(11):4838–42, 1995.CrossRefGoogle Scholar
  131. 131.
    Barillari G, Gendelman R, Gallo RC, Ensoli B. The Tat protein of human immunodeficiency virus type 1, a growth factor for AIDS Kaposi sarcoma and cytokine-activated vascular cells, induces adhesion of the same cell types by using integrin receptors recognizing the RGD amino acid sequence. Proc Natl Acad Sci U S A 90(17):7941–5, 1993.PubMedCrossRefGoogle Scholar
  132. 132.
    Cozen W, Bernstein L, Wang F, Press MF, Mack TM. The risk of angiosarcoma following primary breast cancer. Br J Cancer 81(3):532–6, 1999.PubMedCrossRefGoogle Scholar
  133. 133.
    Hallel-Halevy D, Yerushalmi J, Grunwald MH, Avinoach I, Halevy S. Stewart-Treves syndrome in a patient with elephantiasis. J Am Acad Dermatol 41(2 Pt 2):349–50, 1999.PubMedCrossRefGoogle Scholar
  134. 134.
    Stewart FW, Treves N. Classics in oncology: lymphangiosarcoma in postmastectomy lymphedema: a report of six cases in elephantiasis chirurgica. CA Cancer J Clin 31(5):284–99, 1981.Google Scholar
  135. 135.
    Gill W, Bruce J. Stewart-Treves syndrome. J R Coll Surg Edinb 1968;13(1):34–9.PubMedGoogle Scholar
  136. 136.
    Enzinger F, Weiss S. Soft Tissue Tumors. St. Louis: CV Mosby Co., 1983.Google Scholar
  137. 137.
    Robbins S, Cotran R, Kumar V. Pathologic Basis of Disease. Third Edition ed. Philadelphia, PA: WB Saunders Co., 1984.Google Scholar
  138. 138.
    Gallo RC. The enigmas of Kaposi’s sarcoma. Science 282(5395):1837–9, 1998.PubMedCrossRefGoogle Scholar
  139. 139.
    Gallo RC. Some aspects of the pathogenesis of HIV-1-associated Kaposi’s sarcoma. J Natl Cancer Inst Monogr 23:55–7, 1998.PubMedCrossRefGoogle Scholar
  140. 140.
    Gaffey MJ, Weiss LM. Viral oncogenesis: Epstein-Barr virus. Am J Otolaryngol 11(6):375–81, 1990.PubMedCrossRefGoogle Scholar
  141. 141.
    Grafton WD. Regressing malignant melanoma. J La State Med Soc 146(12):535–9, 1994.PubMedGoogle Scholar
  142. 142.
    Menzies SW, McCarthy WH. Complete regression of primary cutaneous malignant melanoma. Arch Surg 132(5):553–6, 1997.PubMedCrossRefGoogle Scholar
  143. 143.
    Shai A, Avinoach I, Sagi A. Metastatic malignant melanoma with spontaneous and complete regression of the primary lesion. Case report and review of the literature. J Dermatol Surg Oncol 20(5):342–5, 1994.PubMedGoogle Scholar
  144. 144.
    Knowles DM. Immunodeficiency-associated lymphoproliferative disorders. Mod Pathol 12(2):200–17, 1999.PubMedGoogle Scholar
  145. 145.
    Penn I. Kaposi’s sarcoma in transplant recipients. Transplantation 64(5):669–73, 1997.PubMedCrossRefGoogle Scholar
  146. 146.
    Matsushima AY, Strauchen JA, Lee G, et al. Posttransplantation plasmacytic proliferations related to Kaposi’s sarcoma-associated herpesvirus. Am J Surg Pathol 23(11):1393–400, 1999.PubMedCrossRefGoogle Scholar
  147. 147.
    Cattelan AM, Calabro ML, Aversa SM, et al. Regression of AIDS-related Kaposi’s sarcoma following antiretroviral therapy with protease inhibitors: biological correlates of clinical outcome [In Process Citation]. Eur J Cancer 35(13):1809–15, 1999.PubMedCrossRefGoogle Scholar
  148. 148.
    Timmerman JM, Levy R. Dendritic cell vaccines for cancer immunotherapy. Annu Rev Med 50:507–29, 1999.PubMedCrossRefGoogle Scholar
  149. 149.
    Trapeznikov NN, Iavorskii VV, Kadagidze ZG, Malaev SG, Kupin VI. [Immunological reactions of skin melanoma patients to nonspecific and adaptive immunotherapy]. Vopr Onkol 23(8):27–33, 1977.PubMedGoogle Scholar
  150. 150.
    Pitts JM, Maloney ME. Therapeutic advances in melanoma. Dermatol Clin 18(1):157–67, 2000.PubMedCrossRefGoogle Scholar
  151. 151.
    McMasters KM, Sondak VK, Lotze MT, Ross MI. Recent advances in melanoma staging and therapy. Ann Surg Oncol 6(5):467–75, 1999.PubMedCrossRefGoogle Scholar
  152. 152.
    Marchand M, van Baren N, Weynants P, et al. Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA- Al. Int J Cancer 80(2):219–30, 1999.PubMedCrossRefGoogle Scholar
  153. 153.
    Butterfield LH, Jilani SM, Chakraborty NG, et al. Generation of melanoma-specific cytotoxic T lymphocytes by dendritic cells transduced with a MART-1 adenovirus. J Immunol 161(10):5607–13, 1998.PubMedGoogle Scholar
  154. 154.
    Greene JF, Jr., Townsend JSt, Amoss MS, Jr. Histopathology of regression in sinclair swine model of melanoma [see comments]. Lab Invest 71(1):17–24, 1994.PubMedGoogle Scholar
  155. 155.
    Hajduch M, Kolar Z, Novotny R, et al. Induction of apoptosis and regression of spontaneous dog melanoma following in vivo application of synthetic cyclin-dependent kinase inhibitor olomoucine. Anticancer Drugs 8(10):1007–13, 1997.PubMedCrossRefGoogle Scholar
  156. 156.
    Zorn E, Hercend T. A natural cytotoxic T cell response in a spontaneously regressing human melanoma targets a neoantigen resulting from a somatic point mutation. Eur J Immuno1 29(2):592–601, 1999.CrossRefGoogle Scholar
  157. 157.
    Schulz TF, Moore PS. Kaposi’s sarcoma-associated herpesvirus: a new human tumor virus, but how? [see comments]. Trends Microbiol 7(5):196–200, 1999.PubMedCrossRefGoogle Scholar
  158. 158.
    Herndier B. Cancer (or lack thereof) and viruses [letter; comment]. Trends Microbiol 7(7):269–70, 1999.PubMedCrossRefGoogle Scholar
  159. 159.
    Schulz TF, Moore PS. Response from schulz and moore. Trends Microbiol 7(7):269–70, 1999.PubMedCrossRefGoogle Scholar
  160. 160.
    Gao SJ, Zhang YJ, Deng JH, Rabkin CS, Flore O, Jenson HB. Molecular polymorphism of Kaposi’s sarcoma-associated herpesvirus (Human herpesvirus 8) latent nuclear.antigen: evidence for a large repertoire of viral genotypes and dual infection with different viral genotypes [published erratum appears in J Infect Dis 1999 Nov;180(5):17561. J Infect Dis 180(5):1466–76, 1999.PubMedCrossRefGoogle Scholar
  161. 161.
    Rabkin C, Janz S, Lash A, et al. Monoclonal origin of multicentric Kaposi’s sarcoma lesions. N Engl J Med 336(14):988–993, 1997.PubMedCrossRefGoogle Scholar
  162. 162.
    Delabesse E, Oksenhendler E, Lebbe C, Verola O, Varet B, Turhan AG. Molecular analysis of conality in Kaposi’s sarcoma. J Clin Pathol 50(8):664–8, 1997.PubMedCrossRefGoogle Scholar
  163. 163.
    Gill PS, Tsai YC, Rao AP, et al. Evidence for multiclonality in multicentric Kaposi’s sarcoma. Proc Natl Acad Sci U S A 95(14):8257–61, 1998.PubMedCrossRefGoogle Scholar
  164. 164.
    Chadburn A, Cesarman E, Liu YF, et al. Molecular genetic analysis demonstrates that multiple posttransplantation lymphoproliferative disorders occurring in one anatomic site in a single patient represent distinct primary lymphoid neoplasms. Cancer 75(11):2747–56, 1995.PubMedCrossRefGoogle Scholar
  165. 165.
    Lipford EH, Smith HR, Pittaluga S, Jaffe ES, Steinberg AD, Cossman J. Clonality of angioimmunoblastic lymphadenopathy and implications for its evolution to malignant lymphoma. J Clin Invest 79(2):637–42, 1987.PubMedCrossRefGoogle Scholar
  166. 166.
    Cossman J, Uppenkamp M, Sundeen J, Coupland R, Raffeld M. Molecular genetics and the diagnosis of lymphoma. Arch Pathol Lab Med 112(2):117–27, 1988.PubMedGoogle Scholar
  167. 167.
    Cossman J, Uppenkamp M, Andrade R, Medeiros LJ. T-cell receptor gene rearrangements and the diagnosis of human T-cell neoplasms. Crit Rev Oncol Hematol 10(3):267–81, 1990.PubMedCrossRefGoogle Scholar
  168. 168.
    Herndier BG. Surgical pathology of HIV associated lymphoproliferations. Cancer Sury 10:135–49, 1991.Google Scholar
  169. 169.
    Herndier BG, Shiramizu BT, McGrath MS. AIDS associated non-Hodgkin’s lymphomas represent a broad spectrum of monoclonal and polyclonal lymphoproliferative processes. Curr Top Microbiol Immunol 182:385–94, 1992.PubMedCrossRefGoogle Scholar
  170. 170.
    Meeker TC, Shiramizu B, Kaplan L, et al. Evidence for molecular subtypes of HIV-associated lymphoma: division into peripheral monoclonal, polyclonal and central nervous system lymphoma. Aids 5(6):669–74, 1991.PubMedCrossRefGoogle Scholar
  171. 171.
    Shiramizu B, Herndier B, Meeker T, Kaplan L, McGrath M. Molecular and immunophenotypic characterization of AIDS-associated, Epstein-Barr virus-negative, polyclonal lymphoma [see comments]. J Clin Oncol 10(3):383–9, 1992.PubMedGoogle Scholar
  172. 172.
    Kaplan LD, Shiramizu B, Herndier B, et al. Influence of molecular characteristics on clinical outcome in human immunodeficiency virus-associated non-Hodgkin’s lymphoma: identification of a subgroup with favorable clinical outcome. Blood 85(7):1727–35, 1995.PubMedGoogle Scholar
  173. 173.
    McGrath MS, Shiramizu B, Meeker TC, Kaplan LD, Herndier B. AIDS-associated polyclonal lymphoma: identification of a new HIV- associated disease process. J Acquir Immune Defic Syndr 4(4):408–15, 1991.PubMedGoogle Scholar
  174. 174.
    Frizzera G, Hanto DW, Gajl-Peczalska KJ, et al. Polymorphic diffuse B-cell hyperplasias and lymphomas in renal transplant recipients. Cancer Res 41(11 Pt 1):4262–79, 1981.PubMedGoogle Scholar
  175. 175.
    Hanto DW, Frizzera G, Purtilo DT, et al. Clinical spectrum of lymphoproliferative disorders in renal transplant recipients and evidence for the role of Epstein-Barr virus. Cancer Res 41(11 Pt 1):4253–61, 1981.PubMedGoogle Scholar
  176. 176.
    Hanto DW, Birkenbach M, Frizzera G, Gajl-Peczalska KJ, Simmons RL, Schubach WH. Confirmation of the heterogeneity of posttransplant Epstein-Barr virus-associated B cell proliferations by immunoglobulin gene rearrangement analyses. Transplantation 47(3):458–64, 1989.PubMedCrossRefGoogle Scholar
  177. 177.
    Knowles DM, Cesarman E, Chadburn A, et al. Correlative morphologic and molecular genetic analysis demonstrates three distinct categories of posttransplantation lymphoproliferative disorders. Blood 85(2):552–65, 1995.PubMedGoogle Scholar
  178. 178.
    Weiss LM, Spagnolo DV. Assessment of clonality in lymphoid proliferations [comment]. Am J Pathol 142(6):1679–82, 1993.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Brian Herndier
    • 1
  • Don Ganem
    • 1
  1. 1.University of California San FrancisoUSA

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