Ki67 is a better marker than PRAME in risk stratification of BAP1-positive and BAP1-loss uveal melanomas.

Abstract

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