Skip to main content
Log in

Proliferation and apoptosis in the evolution of endemic and acquired immunodeficiency syndrome-related Kaposi's sarcoma

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Kaposi's sarcoma (KS) is a multifocal lesion that occurs predominantly in the skin, most frequently in people infected with HIV-1, and that evolves through early stages (patch and plaque) to a tumor-like late stage (nodular). Both, endemic African (EKS) and AIDS-associated (AKS) KS expressed human herpesvirus 8 (HHV-8) as shown by PCR. By immunohistochemistry the expression of cellular Bcl-2 and c-myc was confined in early stages of both EKS and AKS to relatively few endothelial cells (EC) whereas in nodular KS most of spindle cells (SC) strongly expressed both genes. CD40 was usually strongly expressed in SC at all KS stages as well as in EC of non-involved tissue whereas CD40L (CD154) was not demonstrable. Fas (CD95) was moderately to weakly expressed by SC whereas p53 and Waf-1 were found in less than 5% of the SC. In both AKS and EKS at nodular stage almost no apoptotic SC were detected. In most AKS and EKS low levels of cell proliferation were seen but AKS showed consistently higher values compared to EKS. All clinical types and stages of KS showed a diploid cellular DNA content by flow cytometric analysis of microselected lesions. Thus, we conclude that KS during evolution represents diploid, probably reactive, cell proliferation, which progressively increases the expression of strong cellular and also viral (HHV-8) antiapoptotic factors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Kaaya EEet al. Expression of adhesion molecules in endemic and epidemic Kaposi's sarcoma.Histopathology 1996;29: 337–346.

    Article  CAS  PubMed  Google Scholar 

  2. Kaaya EEet al. Spindle cell ploidy and proliferation in endemic and epidemic Kaposi's sarcoma.Eur J Cancer 1992;28A: 1890–1894.

    Article  CAS  PubMed  Google Scholar 

  3. Chang Yet al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma.Science 1994;266: 1865–1869.

    Article  CAS  PubMed  Google Scholar 

  4. Schalling M, Ekman M, Kaaya EE, Linde A, Biberfeld P. A role of a new herpes virus (KSHV) in different forms of Kaposi's sarcoma.Nature Med 1995;1: 701–702.

    Article  Google Scholar 

  5. Biberfeld P, Ensoli B, Stürzl M, Schulz T. KSHV/HHV-8, cytokines, growth factors and HIV in pathogenesis of Kaposi's sarcoma.Curr Opin Infec Dis 1998;11: 97–105.

    Article  CAS  Google Scholar 

  6. Gaidano G, Castaños-Vélez E, Biberfeld P. Lymphoid disorders associated with HHV-8 infection: facts and contentions.Med Oncol 1999;16: 8–12.

    Article  CAS  PubMed  Google Scholar 

  7. Nicholas Jet al. A single 13-kilobase divergent locus in the Kaposi's sarcoma-associated herpesvirus (human herpes virus 8) genome contains nine open reading frames that are homologous to or related to cellular proteins.J Virol 1997;71: 1963–1974.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Heiden T, Wang N, Tribukait B. An improved Hedley method for preparation of paraffin-embedded tissues for flow cytometric analysis of ploidy and S-phase.Cytometry 1991;12: 614–621.

    Article  CAS  PubMed  Google Scholar 

  9. Stürzl Met al. Expression of K13/v-FLIP gene of human herpesvirus 8 and apoptosis in Kaposi's sarcoma spindle cells.J Natl Cancer Inst 1999;91: 1725–1733.

    Article  PubMed  Google Scholar 

  10. Reed J. Double identity for proteins of the Bcl-2 family.Nature 1997;387: 773–776.

    Article  CAS  PubMed  Google Scholar 

  11. Morris CBet al. Immunohistochemical detection of bcl-2 in AIDS-associated and classical Kaposi's sarcoma.Am J Path 1996;148: 1055–1063.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Dada MAet al. The immunoexpression of bcl-2 and p53 in Kaposi's sarcoma.Histopathology 1996;29: 159–163.

    Article  CAS  PubMed  Google Scholar 

  13. Simonart Tet al. Overexpression of Bcl-2 in Kaposi's sarcoma derived cells.J Invest Dermatol 1998;111: 349–353.

    Article  CAS  PubMed  Google Scholar 

  14. Pillay P, Chetty R, Reddy R. Bcl-2 and p53 immunoprofile in Kaposi's sarcoma.Pathol Oncol Res 1999;5: 17–20.

    Article  CAS  PubMed  Google Scholar 

  15. Cheng EHYet al. A Bcl-2 homologue encoded by Kaposi,s sarcoma-associated virus, human herpesvirus 8, inhibits apoptosis but does not hetetodimerize with Bax or Bak.Proc Natl Acad Sci USA 1997;94: 690–694.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Pammer Jet al. CD40 antigen is expressed by endothelial cells and tumor cells in Kaposi's sarcoma.Am J Pathol 1996;148: 1387–1396.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Thome Met al. Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors.Nature 1997;386: 517–521.

    Article  CAS  PubMed  Google Scholar 

  18. Djerbi Met al. The inhibitor of death-receptor signaling FLIP defines new class of tumour progression factors.J Exp Med 1999;190: 1025–1032.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Spandidos DAet al. Ras, C-myc and c-erbB-2 expression in non-AIDS Mediterranean Kaposi's sarcoma.Anticancer Res 1990;10: 1619–1625.

    CAS  PubMed  Google Scholar 

  20. Thompson EB. The many roles of c-Myc in apoptosis.Ann Rev Physiol 1998;60: 575–600.

    Article  CAS  Google Scholar 

  21. Koster Ret al. Consensus-interferon and platelet-derived growth factor adversely regulate proliferation and migration of Kaposi's sarcoma cells by control of c-myc expression.Am J Pathol 1996;149: 1871–1885.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Brambilla Eet al. Apoptosis-related factors p53, Bcl-2 and Bax in neuroendocrine lung tumors.Am J Pathol 1996;149: 1941–1952.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Bergman Ret al. An immunohistochemical study of p53 protein expression in classical Kaposi's sarcoma.Am J Dermatopathol 1996;18: 367–370.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to P Biberfeld.

Additional information

These authors have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kaaya, E., Castaños-Vélez, E., Heiden, T. et al. Proliferation and apoptosis in the evolution of endemic and acquired immunodeficiency syndrome-related Kaposi's sarcoma. Med Oncol 17, 325–332 (2000). https://doi.org/10.1007/BF02782199

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02782199

Keywords

Navigation