Association of Age With Gene Expression Profile (GEP) Class and Preferentially Expressed Antigen in Melanoma (PRAME) Expression Status in Uveal Melanoma

Background and Objective: The purpose of this study was to assess the association between patient age and two high-risk molecular features in uveal melanoma (UM): class 2 gene expression profile (GEP) and positive preferentially expressed antigen in melanoma (PRAME) expression status. Patients and Methods: This retrospective study included 481 UM patients who underwent molecular profiling. Multivariate logistic regression evaluated associations between GEP class 2 or positive PRAME expression status and demographic and clinical features. Nonlinear effects of age on GEP class were assessed using a 3-knot restricted cubic spline. A multivariable model using age cohorts was employed to examine GEP class 2 risk across clinically meaningful age groups. Results: Multivariate analysis confirmed that older age is associated with GEP class 2 profile. The nonlinear component of the spline model reached borderline significance ( P = .07) and the spline model demonstrated a superior fit compared to standard multivariable linear regression, identifying a transition in GEP class 2 risk from a plateau to an escalation starting around the sixth decade of life. Multivariable age cohort analysis revealed that patients aged 70 to 79 years had a 2.5-fold increase in the odds of a class 2 tumor, while patients ≥ 80 years of age experienced a 3.6-fold increase compared to patients < 50 years of age. Tumor largest basal diameter and ciliary body involvement were also associated with GEP class and PRAME expression. Both linear and nonlinear models revealed no significant association between age and PRAME expression. Conclusions: Older age is strongly associated with GEP class 2 status, with risk escalating in later life, suggesting that advanced age, particularly greater than 60 to 70 years, should prompt a high index of suspicion in the management of uveal nevi or melanoma.