TY - JOUR
T1 - Gene Expression Profiling and PRAME Status Versus Tumor-Node-Metastasis Staging for Prognostication in Uveal Melanoma
AU - Cai, Louis
AU - Paez-Escamilla, Manuel
AU - Walter, Scott D.
AU - Tarlan, Bercin
AU - Decatur, Christina L.
AU - Perez, Barbara M.
AU - Harbour, J. William
N1 - Funding Information:
Funding/Support: J. William Harbour was supported by the National Institutes of Health (Bethesda, Maryland, USA) R01 CA125970, the Alcon Research Institute (Fort Worth, Texas, USA), Research to Prevent Blindness , Inc Senior Investigator Award (New York, New York, USA), and a generous gift from Dr Mark J. Daily. The Bascom Palmer Eye Institute received funding from National Institutes of Health (Bethesda, Maryland, USA) Core Grant P30EY014801 . Department of Defense (Washington, DC) 329 Grant # W81XWH-13-1-0048 , and a Research to Prevent Blindness Unrestricted Grant (New York, New York, USA). Financial Disclosures: J. William Harbour is the inventor of intellectual property used in the study and receives royalties from its commercialization. He is a paid consultant for Castle Biosciences, licensee of this intellectual property. Scott D. Walter served on an advisory board for Castle Biosciences. The following authors have no financial disclosures: Louis Cai, Manuel Paez-Escamilla, Bercin Tarlan, Christina L. Decatur, and Barbara M. Perez. All authors attest that they meet the current ICMJE criteria for authorship.
Funding Information:
Funding/Support: J. William Harbour was supported by the National Institutes of Health (Bethesda, Maryland, USA) R01 CA125970, the Alcon Research Institute (Fort Worth, Texas, USA), Research to Prevent Blindness, Inc Senior Investigator Award (New York, New York, USA), and a generous gift from Dr Mark J. Daily. The Bascom Palmer Eye Institute received funding from National Institutes of Health (Bethesda, Maryland, USA) Core Grant P30EY014801. Department of Defense (Washington, DC) 329 Grant #W81XWH-13-1-0048, and a Research to Prevent Blindness Unrestricted Grant (New York, New York, USA). Financial Disclosures: J. William Harbour is the inventor of intellectual property used in the study and receives royalties from its commercialization. He is a paid consultant for Castle Biosciences, licensee of this intellectual property. Scott D. Walter served on an advisory board for Castle Biosciences. The following authors have no financial disclosures: Louis Cai, Manuel Paez-Escamilla, Bercin Tarlan, Christina L. Decatur, and Barbara M. Perez. All authors attest that they meet the current ICMJE criteria for authorship.
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/11
Y1 - 2018/11
N2 - 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.
AB - 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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U2 - 10.1016/j.ajo.2018.07.045
DO - 10.1016/j.ajo.2018.07.045
M3 - Article
C2 - 30092184
AN - SCOPUS:85053061303
SN - 0002-9394
VL - 195
SP - 154
EP - 160
JO - American journal of ophthalmology
JF - American journal of ophthalmology
ER -