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Original research
PRDX3 is associated with metastasis and poor survival in uveal melanoma
  1. Pathma Ramasamy1,2,3,
  2. Anne-Marie Larkin2,4,
  3. Annett Linge2,
  4. Damien Tiernan5,
  5. Fionnuala McAree5,
  6. Noel Horgan5,
  7. Paul Moriarty5,
  8. Stephen Beatty6,
  9. Conor C Murphy1,5,
  10. Martin Clynes2,7,
  11. Susan Kennedy8,
  12. Paula Meleady2
  1. 1 Department of Ophthalmology, Royal College of Surgeons in Ireland, Dublin, Ireland
  2. 2 National Institute for Cellular Biotechnology, Dublin, Ireland
  3. 3 Royal Victoria Eye and Ear Hospital, Dublin, Ireland
  4. 4 Department of Life Sciences, Institute of Technology Sligo, Sligo, Ireland
  5. 5 Royal Victoria Eye and Ear Hospital, Dublins, Ireland
  6. 6 Waterford Institute of Technology, Waterford, Ireland
  7. 7 Synthesis and Solid State Pharmaceutical Centre, Science Foundation Ireland, Dublin, Ireland
  8. 8 Histopathology, Royal Victoria Eye and Ear Hospital, Dublin, Ireland
  1. Correspondence to Dr Pathma Ramasamy, Department of Ophthalmology, Royal College of Surgeons in Ireland, Dublin D02 YN77, Ireland; pathmaramasamy{at}rcsi.ie

Abstract

Aims Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, and 40% develop fatal metastatic disease. Overexpression of thioredoxin-dependent peroxidase reductase (PRDX3) has been implicated in several cancers, including prostate, breast, colorectal and lung cancer. The aim of this study was to compare the immunohistochemical expression of PRDX3 in formalin-fixed, paraffin-embedded (FFPE) primary UM tissues of patients who did and did not develop metastatic disease.

Methods Immunohistochemical staining of PRDX3 was performed on FFPE tissue microarray samples of 92 primary UM tumours from patients who did and did not develop metastatic disease. The immunohistochemical staining was assessed by two observers who were blinded to all clinicopathological and cytogenetic details including metastatic/non-metastatic information. Based on a scoring system, expression of PRDX3 was graded as high or low.

Results There were 55 tumours (59.8%) from patients who developed metastatic disease, while 37 (40.2%) were from patients who did not develop metastasis. A statistically significant difference in PRDX3 expression was observed in patients who did and did not develop metastasis (p=0.001). A significant positive correlation between high PRDX3 expression and metastasis was observed (p=0.001). A significant negative correlation between PRDX3 expression and survival was found (p=0.005). Kaplan-Meier survival analysis showed a statistically significant difference in overall survival between tumours that demonstrated low and high expression of PRDX3 (67.61 vs 130.64 months, respectively, p=0.013).

Conclusions High immunohistochemical expression of PRDX3 in primary UM tissue is associated with metastasis and poor survival.

  • uveal melanoma
  • ophthalmology
  • malignant tumours
  • metastasis
  • oncology

https://doi.org/10.1136/jclinpath-2019-206173

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    Footnotes

    • Handling editor Runjan Chetty.

    • Presented at This study was previously published as a thesis by Dr Pathma Ramasamy and is available online.37

    • Funding This research was funded by the Irish Health Research Board (grant no HRA-POR-2013-386) and the Royal Victoria Eye and Ear Research Foundation.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval Ethical approval was obtained from the Research and Ethics Committee of the Royal Victoria Eye and Ear Hospital, Dublin. The research adhered to the tenets of the Declaration of Helsinki.

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

    • Data availability statement Data are available in a public, open access repository.