Revisiting the value of assessing the mitotic rate of choroidal melanoma

Abstract

Abstract Purpose To re‐evaluate mitotic rate (MR) as an indicator of malignancy grade in uveal melanoma (UM) and as a predictor for UM‐related mortality. Methods UM patients treated 1993‐2006 by local resection or enucleation were included. Data on largest basal diameter (LBD), ciliary body involvement, extraocular extension, cell type, closed loops, MR per 40/HPF, cytogenetics were collected. Mortality data were obtained from NHS Cancer Registry. Results 918 patients (520 M; 398 F) had median age of 64.6 yrs with a median follow‐up of 3.46 yrs (range 0.02‐13). The UM had mean diameter of 14.9 mm with ciliary body involvement in 43.0%, epithelioid cells in 63.3%, closed loops in 41.2%, extraocular spread in 11.3%. Cytogenetics in 337 patients showed disomy 3 and 8 in 27%, monosomy 3 in 10.7%, chromosome 8 gains in 24.0%, both these abnormalities in 38.3%. The median MR was 3(range 0‐61, SD 6). High MR correlated with ciliary body involvement (p = 0.001), epithelioid cells(p = 0.009), closed loops(p<0.0001), extraocular spread(p=0.027) & monosomy 3(p<0.0001;Mann‐Whitney). MR also correlated with LBD(p=0.0001; t‐test). Metastatic death occurred in 243 patients (26.7%). Kaplan‐Meier analysis showed MR >4/40 HPF to be associated with increased 10‐year metastatic mortality from 32.5 (95% confidence intervals [CI] 25.7‐39.3) to 65.5 (95% CI 55‐7‐75.4; log rank statistic 53.28, p<0.0001). Cox multivariate analysis showed MR to be an independent predictive factor for metastatic death (p<0.0001). MR was predictive of metastatic death also in patients without detectable monosomy 3 (Log rank statistic 10.38, p = 0.002). Conclusion MR correlates with other known risk factors for metastatic death and independently predicts mortality even when cytogenetics show disomy 3.