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Ki67 is a better marker than PRAME in risk stratification of BAP1-positive and BAP1-loss uveal melanomas
  1. Piotr Donizy1,2,
  2. Mikołaj Spytek3,
  3. Mateusz Krzyziński3,
  4. Krzysztof Kotowski1,
  5. Anna Markiewicz4,
  6. Bozena Romanowska-Dixon4,
  7. Przemyslaw Biecek3,
  8. Mai P Hoang5
  1. 1 Department of Clinical and Experimental Pathology, Wroclaw Medical University, Wroclaw, Poland
  2. 2 Department of Pathology and Clinical Cytology, Jan Mikulicz-Radecki University Hospital, Wroclaw, Poland
  3. 3 Faculty of Mathematics and Information Science, Warsaw University of Technology, Warsaw, Poland
  4. 4 Department of Ophthalmology and Ocular Oncology, Jagiellonian University Medical College, Kraków, Poland
  5. 5 Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Mai P Hoang, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; mhoang{at}mgh.harvard.edu

Abstract

Background Accurate risk stratification of uveal melanoma (UM) patients is important for determining the interval and frequency of surveillance. Loss of BAP1 expression has been shown to be strongly associated with UM-related death and metastasis.

Methods In this study of 164 enucleated UMs, we assessed the prognostic role of preferentially expressed antigen in melanoma (PRAME) expression and Ki67 proliferation index measured by digital quantitation using QuPath programme in patients with BAP1-positive and BAP1-loss UMs.

Results In univariate analyses with log-rank tests and Kaplan-Meier curves, PRAME further stratified only overall survival (OS) in BAP1-positive and BAP1-loss tumour groups. However, Ki67 further stratified both OS and disease-free survival (DFS) in BAP1-positive and BAP1-loss tumour groups. In multivariate analyses, Ki67 percentage and BAP1 were independent survival predictors for both OS and DFS, whereas PRAME was not a significant covariate. In model comparisons, combined Ki67 and BAP1 performed better than combined PRAME and BAP1 in risk-stratifying patients for both OS and DFS. Ki67 was better than PRAME in risk stratification of BAP1-positive UMs. Low Ki67 index correlated with significantly prolonged DFS in BAP1-loss UMs.

Conclusion A panel of Ki67 and BAP1 could be a helpful risk stratification strategy for UM.

  • Pathology
  • Neoplasia
  • Eye (Globe)
  • Diagnostic tests/Investigation

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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Footnotes

  • Contributors PD, MS, MK, PB and MPH performed study concept and design; PD, MS, MK, KK, AM, BR-D, PB and MPH performed acquisition, analysis and interpretation of data; PD, MS, MK, PB and MPH performed development of methodology; PD, KK, AM, BR-D and MPH performed data analysis; MS, MK, PB and MPH performed statistical analyses; PD, MS, MK, KK, AM, BR-D, PB and MPH provided technical and material support. PD, MS and MPH wrote the original manuscript draft. MPH is the guarantor.

  • Funding Funding was awarded to PD by the Polish Ministry of Education and Science in the 'Regional Initiative of Excellence' program for the years 2019-2022, project number 016/RID/2018/19.

  • Competing interests None declared.

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

  • 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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