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Expression of cancer-testis antigens (MAGE-A1, MAGE-A3/6, MAGE-A4, MAGE-C1 and NY-ESO-1) in primary human uveal and conjunctival melanoma
  1. J A Errington1,
  2. R M Conway2,
  3. N Walsh-Conway2,
  4. J Browning3,
  5. C Freyer3,
  6. J Cebon3,
  7. M C Madigan1,2
  1. 1School of Optometry & Vision Science, University of New South Wales, Sydney, New South Wales, Australia
  2. 2Save Sight Institute, University of Sydney, Sydney, New South Wales, Australia
  3. 3Ludwig Institute for Cancer Research, Melbourne Centre for Clinical Sciences, Austin Health, Heidelberg, Victoria, Australia
  1. Correspondence to Dr Michele C Madigan, Optometry & Vision Science, University of New South Wales, RMB North, 3.023, NSW 2052, Australia; m.madigan{at}unsw.edu.au

Abstract

Aim Metastatic disease in ocular melanoma remains untreatable, is associated with late detection and is resistant to conventional systemic therapies. Many tumours including cutaneous melanoma express specific cancer-testis (CT) antigens and vaccines targeting these antigens can induce T-cell-mediated and humoural immune responses. The authors examined primary uveal and conjunctival melanomas for expression of CT antigens to assess their potential as targets for ocular melanoma immunotherapy.

Methods Paraffin-embedded uveal (n=32) and conjunctival (n=15) melanomas were assessed by immunohistochemistry for melanocyte differentiation antigens (gp100, Melan-A/MART-1 and tyrosinase), and CT antigens (MAGE-A1, MAGE-A3/6, MAGE-A4, MAGE-C1 and NY-ESO-1).

Results Melanoma differentiation antigens, gp100, Melan-A/MART1 and tyrosinase, were expressed in >75% of tumour cells in all uveal and conjunctival melanomas tested. Expression of all five CT antigens tested was low in uveal melanomas, and when present, stained <25% of the tumour cells. MAGE-A1, MAGE-A4 and NY-ESO-1 were expressed in <10% of tumour cells in conjunctival melanomas, while MAGE-C1 and MAGE-A3/6 were expressed in ∼20% and ∼35% of tumour cells in this malignancy, respectively, with variable expression levels.

Conclusions Uveal and conjunctival melanomas consistently expressed high levels of the differentiation antigens (gp100, Melan-A/MART1 and tyrosinase). However, compared with other tumours, including cutaneous melanoma, only low levels of CT antigens were found in ocular melanomas. These observations suggest that immunotherapy directly targeting the CT antigens studied may not be effective for ocular melanoma.

  • Ocular melanoma
  • CT antigen
  • tumour vaccine
  • immunotherapy
  • pathology
  • anatomy
  • degeneration
  • choroid
  • retina

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Footnotes

  • Funding The authors acknowledge support from The Claffy Foundation, Sydney Hospital/Sydney Eye Hospital and the Sydney Foundation for Medical Research (RMC, NW-C, MCM); the National Health & Medical Research Council (NHMRC), Australia, Melanoma Research Alliance, the Cancer Vaccine Collaborative, New York, the Victorian Cancer Agency and the Ludwig Institute for Cancer Research as well as Operational Infrastructure Support Program funding of the Victorian Government and NHMRC Independent Research Institutes Infrastructure Support Scheme.

  • Competing interests None.

  • Ethics approval Ethics approval was provided by the South Eastern Sydney and Illawarra Health Human Research Ethics Committee and Austin Health Human Research Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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