Gene Expression Profiling and PRAME Status Versus Tumor-Node-Metastasis Staging for Prognostication in Uveal Melanoma

Abstract

To compare the prognostic accuracy of gene expression profiling (GEP) combined with PRAME status vs the clinical Tumor-Node-Metastasis (TNM) staging in patients with uveal melanoma (UM). Retrospective cohort study. The study included 240 consecutive patients with UM. Tumors were assessed for GEP status (Class 1 or Class 2) using a validated 15-gene assay and PRAME expression status using quantitative polymerase chain reaction. TNM staging was according to the American Joint Committee on Cancer 8th edition. Statistical analysis included univariate and multivariate Cox proportional hazard models. Metastasis was the primary endpoint. GEP was Class 1 in 128 (53.3%) cases and Class 2 in 112 (46.7%) cases. PRAME status was negative in 157 (65.4%) cases and positive in 83 (34.6%) cases. TNM was stage I in 26 (10.8%) cases, IIA in 67 (27.9%) cases, IIB in 50 (20.8%) cases, IIIA in 59 (24.6%) cases, and IIIB in 38 (15.8%) cases. Metastatic disease was detected in 59 (24.6%) cases after median follow-up of 29months (mean 42months; range 1-195months). Variables associated with metastasis included (in order of decreasing significance): GEP class (P= 1.5× 10-8), largest basal tumor diameter (P= 2.5× 10-6), PRAME status (P= 2.6× 10-6), and TNM stage (P= 3.7× 10-6). The prognostic accuracy of an optimized 3-category GEP/PRAME model (P= 8.6× 10-14) was superior to an optimized TNM model (P= 1.3× 10-5). In UM, molecular prognostic testing using GEP and PRAME provides prognostic accuracy that is superior to TNM staging.