Dark tumour pigmentation in uveal melanoma predicts poor prognosis independently of size but not independently of chromosome 3 and 8q status

Abstract

Purpose : Heavy pigmentation is known to be a prognostic risk factor in uveal melanoma (UM). We analysed which parameters (genetic status or tumour size) correlated with tumour pigmentation and whether pigmentation should be included in prognostic tests.

Methods : Retrospective comparison of clinical, histopathological and genetic features and survival in UM in a cohort of 1058 patients, enucleated between 1972 and 2021. Tumour pigmentation was scored macroscopically on a 4-point scale (unpigmented to heavily pigmented) and two groups were subsequently created (unpigmented and lightly-pigmented vs moderately- and heavily-pigmented). Cox regression and log-rank test were used for survival analysis, chi-square test was used for correlation analysis

Results : In our large UM cohort, darker tumours have a shorter UM-related survival than lighter tumours (p<0.001). The percentage of tumours with an epithelioid cell type and high AJCC class is higher in dark tumours than in light ones (p=0.001 for both factors). Kaplan-Meier curves computed after splitting the cohort based on AJCC stage and on cell type show that darker tumours have a significantly worse prognosis in both relatively small UM (low AJCC stage, p<0.001) and large UM (high AJCC stage, p=0.028) and in UM with epithelioid cells (p<0.001). Cox regression shows that, when correcting for AJCC class and cell type, tumour pigmentation is still a significant prognostic factor. The percentage of tumours with monosomy 3 or 8q gain increased with increasing pigmentation as well (p<0.001 for both factors). Cox regression showed that when chromosome 3 status and pigmentation are both included, pigmentation is not an independent prognostic indicator.

Conclusions : Our analyses show that dark tumour pigmentation is related to features of bad prognosis in UM (epithelioid cell type, higher AJCC stage, monosomy 3 and chromosome 8q gain). Furthermore, dark tumour pigmentation is related to poor prognosis independently of tumour size and cell type. Pigmentation should be added to prognostic analyses, especially when genetic testing is not available.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Survival in 1054 UM enucleated cases with different degrees of tumour pigmentation, in the total cohort (a), in UM with low and high AJCC stage (b), in spindle and epithelioid UM (c), and in Disomy 3 and Monosomy 3 populations (d).