Archives of Dermatological Research

, Volume 301, Issue 9, pp 673–679

Melanoma gene expression and clinical course

  • M. Vourc’h-Jourdain
  • C. Volteau
  • J. M. Nguyen
  • A. Khammari
  • Brigitte Dreno
Original Paper

Abstract

Evidence for the in vitro lymphocyte response against autologous melanoma has been accumulating over the past 10 years, leading to the identification of numerous melanoma-associated antigens recognised by T cells. These antigens are targets for specific immunotherapy protocols. However, their expression is heterogeneous during tumour progression and may contribute to therapeutic escape mechanisms and disease progression. This study was designed to chart the importance of these escape mechanisms, and to assess the relationship between gene expression and the clinical profile (especially survival data) of patients with melanoma. We studied the expression of certain melanoma genes in tissue biopsies from 202 patients using reverse transcriptase-polymerase chain reaction (RT-PCR). The evaluated genes were Melan-A, tyrosinase, Na-17A, MAGE-1, MAGE-3 and Ny-ESO-1. We then correlated the results to the patients’ survival data. 202 samples (cutaneous, nodal and visceral biopsies) were analysed by RT-PCR. No relationship was found between clinical data and gene expression. No relationship was found between survival data and gene expression, when samples of all stages were combined in the analysis. However, interactions between gene expression and disease stage were significant. When stage III samples alone were considered, MAGE-3 expression alone or in association with the expression of the other tumour-specific genes was found to be significantly associated with a higher disease-free survival (respectively, P = 0.0349; 0.007). Our results provided no evidence for a relationship between gene expression and clinical data, or between gene expression and survival data. However, with regard to certain sub-groups, such as stage III samples, tumour gene expression was significantly associated with survival.

Keywords

Melanoma antigen-encoding genes Melanoma Survival Prognosis 

References

  1. 1.
    Balch CM, Buzaid AC, Soong SJ et al (2001) Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 19:3635–3648PubMedGoogle Scholar
  2. 2.
    Barrow C, Browning J, Macgregor D et al (2006) Tumor antigen expression in melanoma varies according to antigen and stage. Clin Cancer Res 12:673–678. doi:10.1158/1078-0432.CCR-05-1544 CrossRefGoogle Scholar
  3. 3.
    Bulliard JL (2000) Site-specific risk of cutaneous malignant melanoma and pattern of sun exposure in New Zealand. Int J Cancer 85:627–632PubMedCrossRefGoogle Scholar
  4. 4.
    De Vries JJ, Smeets M, de Graaf R et al (2001) Expression of gp100, MART-1, tyrosinase, and S100 in paraffin-embedded primary melanomas and locoregional, lymph node, and visceral metastases: implications for diagnosis and immunotherapy. A study conducted by the EORTC Melanoma Cooperative Group. J Pathol 193(1):13–20PubMedCrossRefGoogle Scholar
  5. 5.
    Enk CD, Lotem M, Gimon Z (2004) Molecular detection of MART1, tyrosinase and MIA in peripheral blood, lymph nodes and metastatic sites of stage III/IV melanoma patients. Melanoma Res 14(5):361–365PubMedCrossRefGoogle Scholar
  6. 6.
    Farthmann B (1998) RT-PCR tyrosinase–mRNA–positive cells in peripheral blood: evaluation strategy and correlation with known prognostic markers in 123 melanoma patients. J Invest Dermatol 110(3):263–267PubMedCrossRefGoogle Scholar
  7. 7.
    Hsueh EC, Nathanson L, Foshag LJ et al (1999) Active specific immunotherapy with polyvalent melanoma cell vaccine for patients with in-transit melanoma metastases. Cancer 85:2160–2169PubMedCrossRefGoogle Scholar
  8. 8.
    Jäger E, Ringhoffer M, Altmannsberger M et al (1997) Immunoselection in vivo: independent loss of CMH class I and melanocyte differentiation antigen expression in metastatic melanoma. Int J Cancer 71:142–147PubMedCrossRefGoogle Scholar
  9. 9.
    Jäger E, Ringhoffer M, Dienes HP et al (1996) Granulocyte–macrophage-colony-stimulating factor enhances immune responses to melanoma-associated peptides in vivo. Int J Cancer 67:54–62PubMedCrossRefGoogle Scholar
  10. 10.
    Morton DL, Barth A (1996) Vaccine therapy for malignant melanoma. CA Cancer J Clin 46:225–244PubMedCrossRefGoogle Scholar
  11. 11.
    Morton D, Foshag LJ, Hoon DS et al (1992) Prolongation of survival in metastatic melanoma after active specific immunotherapy with a new polyvalent melanoma vaccine. Ann Surg 216:463–482PubMedCrossRefGoogle Scholar
  12. 12.
    Parisi AV, Kimlin MG, Lester R, Turnbull D (2003) Lower body anatomical distribution of solar ultraviolet radiation on the human form in standing and sitting postures. J Photochem Photobiol B 69:1–6PubMedCrossRefGoogle Scholar
  13. 13.
    Parmiani G, Castelli C, Dalerba P et al (2002) Cancer immunotherapy with peptide-based vaccines: what have we achieved? Where are we going? J Natl Cancer Inst (Bethesda) 94:805–818Google Scholar
  14. 14.
    Rigel DS (2008) Cutaneous ultraviolet exposure and its relationship to the development of skin cancer. J Am Acad Dermatol 58(S2):S129–S132PubMedCrossRefGoogle Scholar
  15. 15.
    Sarantou T, Chi DD, Garrison DA et al (1997) Melanoma associated antigens as messenger RNA detection markers for melanoma. Cancer Res 57:1371–1376PubMedGoogle Scholar
  16. 16.
    Scheibenbogen C, Nagorsen D, Seliger B et al (2002) Long term freedom from recurrence in 2 stage melanoma patients following vaccination with tyrosinase peptides. Int J Cancer 99:403–408PubMedCrossRefGoogle Scholar
  17. 17.
    Takeuchi H, Kuo C, Morton DL et al (2003) Expression of differentiation Melanoma-associated antigen genes is associated with favorable disease outcome in advanced-stage melanomas. Cancer Res 63:441–448PubMedGoogle Scholar
  18. 18.
    Trefzer U, Hofmann M, Reinke S (2006) Concordant loss of melanoma differentiation antigens in synchronous and asynchronous melanoma metastases: implications for immunotherapy. Melanoma Res 16(2):137–145PubMedCrossRefGoogle Scholar
  19. 19.
    Velasquez EF, Jungblut AA, Yancovitz M et al (2007) Expression of the cancer/testis antigen NY-ESO-1 in primary and metastatic malignant melanoma (MM)—correlation with prognostic factors. Cancer Immun 12:7–11Google Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • M. Vourc’h-Jourdain
    • 1
  • C. Volteau
    • 3
  • J. M. Nguyen
    • 3
  • A. Khammari
    • 2
  • Brigitte Dreno
    • 1
    • 2
  1. 1.Unit of Skin Cancer Nantes University HospitalNantesFrance
  2. 2.INSERM U 892, CIC BiothérapieNantesFrance
  3. 3.PIMESP (Pole d’Information Médicale, et d’Evaluation en Santé Publique)NantesFrance

Personalised recommendations