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Prognostic value of TERT promoter mutations in conjunctival melanomas in addition to clinicopathological features
  1. J A van Ipenburg1,
  2. N C Naus2,
  3. H J Dubbink3,
  4. R van Ginderdeuren4,
  5. G S Missotten5,
  6. D Paridaens6,
  7. R M Verdijk7
  1. 1 Pathology, Erasmus MC, Rotterdam, Netherlands
  2. 2 Ophthalmology, Erasmus MC, Medical Centre, Rotterdam, Netherlands
  3. 3 Erasmus Medical Center, Rotterdam, Zuid-Holland,Netherlands
  4. 4 Department of Ophthalmology and Pathology, University Hospital Leuven, Leuven, Belgium
  5. 5 Ophthalmology, KU Leuven University Hospitals Leuven Gasthuisberg Campus Hospital Pharmacy, Leuven, Flanders, Belgium
  6. 6 Rotterdam Eye Hospital, Rotterdam, Netherlands
  7. 7 Pathology, Erasmus University Medical Center, Rotterdam, Netherlands
  1. Correspondence to Robert M M Verdijk, Department of Pathology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands, PO Box 2040, Rotterdam 3000CA, The Netherlands; r.verdijk{at}erasmusmc.nl/ j.vanipenburg{at}erasmusmc.nl

Abstract

Aims To evaluate the prognostic value of clinical, histopathological and molecular features and to relate different treatment modalities to clinical outcome in conjunctival melanomas (CM).

Methods Retrospective review of clinical, histopathological and BRAF V600E and telomerase reverse transcriptase (TERT) promoter mutation status and treatment modalities, correlated to recurrence and metastasis in 79 patients with CM, diagnosed between 1987 and 2015 in three tertiary referral centres in the Netherlands and Belgium.

Results Out of 78 evaluable patients, recurrences occurred in 16 patients and metastasis in 12 patients (median follow-up time 35 months (0–260 months)). Tumour thickness >2 mm, pT status, the presence of epithelioid cells, ulceration and mitoses was significantly correlated with metastasis (p value 0.046, 0.01, 0.02, 0.001 and 0.003, respectively). Furthermore, CM frequently harbour BRAF V600E and TERT promoter mutations (29% and 43%, respectively). TERT promoter mutations were correlated to shorter metastasis-free survival (p value 0.002). No significant correlation was found for clinical parameters and metastatic disease. Palpebral, forniceal and caruncular melanomas were more prone to develop recurrences (p value: 0.03). Most CM were treated with excision with adjuvant therapy.

Conclusion In line with the recommendations in the Eighth Edition of the American Joint Committee on Cancer Staging for CM, the pathology report should include information about pT status, tumour thickness, presence of epithelioid cells, ulceration and mitoses. Furthermore, information about the presence of a TERT promoter mutation and BRAF V600E mutation is of interest for therapeutic decision making. The presence of a TERT promoter mutation is correlated to metastatic disease.

  • Conjunctiva
  • Diagnostic tests/Investigation
  • Neoplasia
  • Pathology
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Footnotes

  • Contributors Design of the study: JI, RMMV and DP. Data acquisition: JI, NCN, HJD, RG, GSM and DP. Data interpretation and critical revision and approval of the manuscript: all authors. Drafting the manuscript: JI.

  • Funding This study was funded by ‘Stichting Nederlands Oogheelkundig Onderzoek’ (grant no.: 2013–2021) and ‘Stichting Wetenschappelijk Oogheelkundig Onderzoek’ (grant no.: 2016–2017).

  • Competing interests None declared.

  • Ethics approval This research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki and the ‘Code of Conduct for Responsible Use of Human Tissue and Medical Research’ that applies to this medical research. Furthermore, for this study, Medical Ethics Committee approval was obtained from Medical Ethics Committee (Erasmus MC-University Medical Center, Rotterdam, The Netherlands: Reference 67865) and European Data Protection Directive (95/46/EC, University Hospital Leuven, Leuven, Belgium: Reference S60279).

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

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplemental information.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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