Skip to main content

Advertisement

SpringerLink
Log in

PGP 9.5 neuronal marker may differentiate immunohistochemically HIV-related from Mediterranean and immunosuppression-associated Kaposi’s sarcoma

  • Original Paper
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

Mediterranean Kaposi’s sarcoma (MKS), HIV-related KS (HIV-KS) and immunosuppression-associated KS (IS-KS), caused by human herpes virus 8 (HHV-8), share similar histological features. The aim of this study was to investigate differences in epidermal nerve fibers (ENFs) between the three KS types and controls. Skin biopsies from 23 HIV-KS, 16 MKS, 28 IS-KS patients and 18 controls, age-gender matched, were immunostained with PGP 9.5; ENFs in upper epidermal layer (EL) and penetrating the basement membrane were measured. The mean number of nerve fibers penetrating ENFs was significantly lower in HIV-KS (p < 0.001) compared to all other groups. MKS and IS-KS had comparable ENFs but lower than controls (p < 0.00 1). In the upper EL all groups had comparable ENFs and lower than controls. In conclusion, HIV-KS can be distinguished histologically from other types, by counting ENFs. Moreover, KS is associated with decreased ENFs, which may be a histological reflection of nerve damage. This is even more pronounced in HIV-KS patients and could be explained by a neurotoxic action of HHV-8, HIV, and their co-existence.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Al’Abadie MSK, Senior HJ, Bleehen SS, Gawkrodger DJ (1995) Neuropeptides and general neuronal marker PGP 9.5 in normal skin: an immunohistochemical study. J Eur Acad Dermatol Venereol 5:201–203

    Article  Google Scholar 

  2. Argov Z, Mastaglia FL (1979) Drug-induced peripheral neuropathies. Br Med J 1:663–666

    Article  CAS  PubMed  Google Scholar 

  3. Beral V, Peterman TA, Berkelman RL, Jaffe HW (1990) Kaposi’s sarcoma among persons with AIDS: a sexually transmitted infection? Lancet 335:123–128

    Article  CAS  PubMed  Google Scholar 

  4. Broccolo F, Iuliano R, Careddu AM, Trovato R, Lico S, Blanc PL, Mazzotta F, Ceccherini-Nelli L (2000) Detection of lymphotropic herpesvirus DNA by polymerase chain reaction in cerebrospinal fluid of AIDS patients with neurological disease. Acta Virol 44:137–143

    CAS  PubMed  Google Scholar 

  5. Pardo CA, McArthur JC, Griffin JW (2001) HIV neuropathy: insights in the pathology of HIV peripheral nerve disease. J Peripher Nerv Syst 6:21–27

    Article  CAS  PubMed  Google Scholar 

  6. Center for Disease Control (1992) Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR 41(RR-17):1–19

    Google Scholar 

  7. Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS (1994) Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science 266:1865–1869

    Article  CAS  PubMed  Google Scholar 

  8. Chien HF, Tseng TJ, Lin WM, Yang CC, Chang YC, Chen RC, Hsieh ST (2001) Quantitative pathology of cutaneous nerve terminal degeneration in the human skin. Acta Neuropathol (Berl) 102:455–461

    CAS  Google Scholar 

  9. Dalsgaard CJ, Rydh M, Haegerstrand A (1989) Cutaneous innervation in man visualized with protein gene product 9.5 (PGP 9.5) antibodies. Histochemistry 92:385–389

    Article  CAS  PubMed  Google Scholar 

  10. Delli-Bovi P, Curatola AM, Kern FG, Greco A, Ittmann M, Basilico C (1987) An oncogene isolated by transfection of Kaposi’s sarcoma DNA encodes for a growth factor that is a member of the FGF family. Cell 50:729–737

    Article  CAS  PubMed  Google Scholar 

  11. Ablashi DV, Chatlynne LG, Whitman JE Jr, Cesarman E (2002) Spectrum of Kaposi’s sarcoma-associated herpesvirus, or human herpesvirus 8, diseases. Clin Microbiol Rev 15(3):439–464

    Article  PubMed  Google Scholar 

  12. Ensoli B, Gendelman R, Markham P, Fiorelli V, Colombini S, Raffeld M, Cafaro A, Chang HK, Brady JN, Gallo RC (1994) Synergy between basic fibroblast growth factor and HIV-1 Tat protein in induction of Kaposi’s sarcoma. Nature 371:674–680

    Article  CAS  PubMed  Google Scholar 

  13. Fenig E (1998) Classic Kaposi sarcoma: experience at Rabin Medical Center in Israel. J Clin Oncol 21:498–500

    Article  CAS  Google Scholar 

  14. Fernandez-Figueras MT, Puig L, Fernandez-Vasalo A, Esquis M, Montero MA, Ariza A (2000) Immunohistochemical detection of bcl-2 in Kaposi’s sarcoma lesions varies according to histopathologic stage, whereas expression of bcl-x and mcl-1 differs according to human immunodeficiency virus serologic status of patients. Mod Pathol 13:438–445

    Article  CAS  PubMed  Google Scholar 

  15. File K, Bower M (1996) Recent insights into the pathogenesis of Kaposi’s sarcoma: a review article. Br J Cancer 73:1317–1322

    Article  Google Scholar 

  16. Gao SJ, Kingsley L, Li M, Zheng W, Parravicini C, Ziegler J, Newton R, Rinaldo CR, Saah A, Phair J, Detels R, Chang Y, Moore PS (1996) KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi’s sarcoma. Nature Med 2:925–928

    Article  CAS  PubMed  Google Scholar 

  17. Gill PS, Tsai YC, Rao AP, Spruck CH III, Zheng T, Harrington WA Jr, Cheung T, Nathwani B, Jones PA (1998) Evidence for multiclonality in multicentric Kaposi’s sarcoma. Proc Natl Acad Sci USA 95:8257–8261

    Article  CAS  PubMed  Google Scholar 

  18. Grayson W, Pantanowitz L (2008) Histological variants of cutaneous Kaposi’s sarcoma: a review article. Diagn Pathol 25(3):31

    Article  Google Scholar 

  19. Herrmann DN, McDermott MP, Henderso D, Chen L, Akowuah K, Schifitto G (2004) Epidermal nerve fiber density, axonal swelling and QST as predictors of HIV distal sensory neuropathy. Muscle Nerve 29:420–427

    Article  PubMed  Google Scholar 

  20. Icovich J (1998) Classic Kaposi’s sarcoma in Jews living in Israel, 1961–1989: a population-based incidence study. AIDS 12:2067–2072

    Article  Google Scholar 

  21. Luppi M (2000) Bone marrow failure associated with human herpesvirus 8 infection after transplantation. N Engl J Med 343:1378–1385

    Article  CAS  PubMed  Google Scholar 

  22. McCarthy BG, Hsieh ST, Stocks A, Hauer P, Macko C, Cornblath DR, Griffin JW, McArthur JC (1995) Cutaneous innervation in sensory neuropathies: evaluation by skin biopsy. Neurology 102:1848–1855

    Article  Google Scholar 

  23. Melbye M, Cook PM, Hjalgrim H, Begtrup K, Simpson GR, Biggar RJ, Ebbesen P, Schulz TF (1998) Risk factors for Kaposi’s-sarcoma-associated herpesvirus (KSHV/HHV-8) seropositivity in a cohort of homosexual men, 1998–1996. Int J Cancer 77:543–548

    Article  CAS  PubMed  Google Scholar 

  24. Miles SA, Rezai AR, Salazar-Gonzalez JF, Vander Meyden M, Stevens RH, Logan DM, Mitsuyasu RT, Taga T, Hirano T, Kishimoto T (1990) AIDS Kaposi’s sarcoma-derived cells produce and respond to interleukin-6. Proc Natl Acad Sci 87:4068–4072

    Article  CAS  PubMed  Google Scholar 

  25. Miles SA, Martinez-Maza O, Rezai A, Magpantay L, Kishimoto T, Nakamura S, Radka SF, Linsley PS (1992) Oncostatin M as a potent mitogen for AIDS-Kaposi’s sarcoma-derived cells. Science 255(5050):1432–1434

    Article  CAS  PubMed  Google Scholar 

  26. Osmond DH, Buchbinder S, Cheng A, Graves A, Vittinghoff E, Cossen CK, Forghani B, Martin JN (2002) Prevalence of Kaposi sarcoma-associated herpesvirus infection in homosexual men at beginning of and during the HIV epidemic. JAMA 287:221–225

    Article  PubMed  Google Scholar 

  27. Pica F, Volpi A, Barillari G, Fraschetti M, Franzese O, Vullo V, Garaci E (1998) Detection of high nerve growth factor serum levels in AIDS-related and -unrelated Kaposi’s sarcoma patients. AIDS 12:2025–2029

    Article  CAS  PubMed  Google Scholar 

  28. Pica F, Volpi A, Serafino A, Fraschetti M, Franzese O, Garaci E (2000) Autocrine nerve growth factor is essential for cell survival and viral maturation in HHV-8-infected primary effusion lymphoma cells. Blood 95:2905–2912

    CAS  PubMed  Google Scholar 

  29. Pittenger GL, Ray M, Burcus NI, McNulty P, Basta B, Vinik AI (2004) Intraepidermal nerve fibers are indicators of small-fiber neuropathy in both diabetic and nondiabetic patients. Diabetes Care 27:1974–1979

    Article  PubMed  Google Scholar 

  30. Quinlivan EB, Wang RX, Stewart PW, Kolmoltri C, Regamey N, Erb P, Vernazza PL (2001) Swiss HIV Cohort Study. Longitudinal sero-reactivity to human herpesvirus 8 (KSHV) in the Swiss HIV Cohort 4.7 years before KS. J Med Virol 64:157–166

    Article  CAS  PubMed  Google Scholar 

  31. Qunibi W (1998) Serologic association of human herpesvirus eight with posttransplant Kaposi’s sarcoma in Saudi Arabia. Transplantation 65:583–585

    Article  CAS  PubMed  Google Scholar 

  32. Rouah E, Gruber R, Shearer W, Armstrong D, Hawkins EP (1988) Graft-versus-host disease in the central nervous system. A real entity? Am J Clin Pathol 89:543–546

    CAS  PubMed  Google Scholar 

  33. Serraino D, Toma L, Andreoni M, Butto S, Tchangmena O, Sarmati L, Monini P, Franceschi S, Ensoli B, Rezza G (2001) A seroprevalence study of human herpesvirus type 8 (HHV8) in Eastern and Central Africa and in the Mediterranean area. Eur J Epidemiol 17:871–876

    Article  CAS  PubMed  Google Scholar 

  34. Sharma KR, Cross J, Santiago F, Ayyar DR, Burke G III (2002) Incidence of acute femoral neuropathy following renal transplantation. Arch Neurol 59:541–545

    Article  PubMed  Google Scholar 

  35. Simpson GR, Schulz TF, Whitby D, Cook PM, Boshoff C, Rainbow L, Howard MR, Gao SJ, Bohenzky RA, Simmonds P, Lee C, de Ruiter A, Hatzakis A, Tedder RS, Weller IV, Moore PS, Weiss RA (1996) Prevalence of Kaposi’s sarcoma associated herpesvirus infection measured by antibodies to recombinant capsid protein and latent immunofluorescence antigen. Lancet 348:1133–1138

    Article  CAS  PubMed  Google Scholar 

  36. Sirianni MC, Vicenzi L, Fiorelli V, Topino S, Scale E, Uccini S, Angeloni A, Faggioni A, Cerimele D, Cottoni F, Aiuti F, Ensoli B (1998) γ-Interferon production in peripheral blood mononuclear cells and tumor infiltrating lymphocytes from Kaposi’s sarcoma patients: correlation with the presence of human herpesvirus-8 in peripheral blood mononuclear cells and lesional macrophages. Blood 91(3):968–976

    CAS  PubMed  Google Scholar 

  37. Skopelitis E, Aroni K, Kontos AN, Konstantinou K, Kokotis P, Karandreas N, Kordossis T (2007) Early detection of subclinical HIV sensory polyneuropathy using intraepidermal nerve fibre density quantification: association with HIV stage and surrogate markers. Int J STD AIDS 18:856–860

    Article  CAS  PubMed  Google Scholar 

  38. Tappero JW, Conant MA, Wolfe SF, Berger TG (1993) Kaposi’s sarcoma. Epidemiology, pathogenesis, histology, clinical spectrum, staging criteria and therapy. J Am Acad Dermatol 28:371–395

    Article  CAS  PubMed  Google Scholar 

  39. Touloumi G, Kaklamanis L, Potouridou I, Katsika-Hatziolou E, Stratigos J, Mueller N, Hatzakis A (1997) The epidemiologic profile of Kaposi’s sarcoma in Greece prior to and during the AIDS era. Int J Cancer 70(5):538–541

    Article  CAS  PubMed  Google Scholar 

  40. Tschopp J, Thome M, Hofmann K, Meinl E (1998) The fight of viruses against apoptosis. Curr Opin Genet Dev 8(1):82–87

    Article  CAS  PubMed  Google Scholar 

  41. Xerri L, Hassoun J, Planche J, Guigou V, Grob JJ, Parc P, Birnbaum D, de Lapeyriere O (1991) Fibroblast growth factor gene expression in AIDS-Kaposi’s sarcoma detected by in situ hybridization. Am J Pathol 138:9–15

    CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors disclose no conflict of interest.

Author information

Authors and Affiliations

  1. Academic Department of Pathophysiology (AIDS Unit), School of Medicine, National and Kapodestrian University of Athens, Athens, Greece

    Vasileia Xyla, Elias Skopelitis, Panayiotis D. Ziakas, Athanasios Kontos & Theodore Kordossis

  2. Academic Department of Dermatopathology, School of Medicine, National and Kapodestrian University of Athens, Athens, Greece

    Vasileia Xyla, Eleftherios Ioannidis & Kyriaki Aroni

  3. Laikon General University Hospital, 21 Achaias Street, 14564, Kifisia Attikis, Greece

    Elias Skopelitis

Authors
  1. Vasileia Xyla
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elias Skopelitis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Panayiotis D. Ziakas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Athanasios Kontos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eleftherios Ioannidis
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Theodore Kordossis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kyriaki Aroni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elias Skopelitis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xyla, V., Skopelitis, E., Ziakas, P.D. et al. PGP 9.5 neuronal marker may differentiate immunohistochemically HIV-related from Mediterranean and immunosuppression-associated Kaposi’s sarcoma. Arch Dermatol Res 305, 917–923 (2013). https://doi.org/10.1007/s00403-013-1364-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-013-1364-3

Keywords

Search

Navigation