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Comparative Study
. 2018 Nov:195:154-160.
doi: 10.1016/j.ajo.2018.07.045. Epub 2018 Aug 6.

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

Louis Cai  1 , Manuel Paez-Escamilla  1 , Scott D Walter  1 , Bercin Tarlan  1 , Christina L Decatur  1 , Barbara M Perez  1 , J William Harbour  2
Affiliations
Comparative Study

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

Louis Cai et al. Am J Ophthalmol. 2018 Nov.

Abstract

Purpose: 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).

Design: Retrospective cohort study.

Methods: 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.

Results: 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 29 months (mean 42 months; range 1-195 months). 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).

Conclusions: In UM, molecular prognostic testing using GEP and PRAME provides prognostic accuracy that is superior to TNM staging.

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Figures

FIGURE 1.
FIGURE 1.
Kaplan-Meier survival analysis in 240 patients with uveal melanoma using Tumor-Node-Metastasis staging and gene expression profiling/PRAME classification. (Top left) Survival curves are shown using all Tumor-Node-Metastasis stages except stage IV. (Middle left) Comparisons of log-rank statistics are shown between Tumor-Node-Metastasis stages. (Bottom left) Survival curves are shown using optimized Tumor-Node-Metastasis categories. (Top right) Survival curves are shown using all gene expression profiling/PRAME categories. (Middle right) Comparisons of log-rank statistics are shown between gene expression profiling/PRAME categories. (Bottom right) Survival curves are shown using optimized gene expression profiling/PRAME categories.
FIGURE 2.
FIGURE 2.
Kaplan-Meier survival analysis in 180 patients with uveal melanoma with largest basal diameter ≥12 mm. (Left) Survival curves are shown using optimized Tumor-Node-Metastasis categories. (Right) Survival curves are shown using gene expression profiling/PRAME categories.
See this image and copyright information in PMC

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