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Personalized Prognosis of Uveal Melanoma Based on Cytogenetic Profile in 1059 Patients over an 8-Year Period: The 2017 Harry S. Gradle Lecture.

Abstract：

PURPOSE:To determine the personalized rate of uveal melanoma-related metastasis on the basis of individual tumor cytogenetic profile. DESIGN:Retrospective case series. PARTICIPANTS:A total of 1059 patients with uveal melanoma. METHODS:Fine-needle aspiration biopsy (FNAB) for DNA amplification and whole genome array-based assay were performed for analysis of chromosomes 3, 6, and 8. MAIN OUTCOME MEASURES:Melanoma-related metastasis. RESULTS:The mean patient age was 57 years, and most were white (1026/1059, 97%). The melanoma involved the choroid (938/1059, 89%), ciliary body (85/1059, 8%), or iris (36/1059, 3%), with 19% being macular in location. The mean largest basal diameter was 11 mm (median, 12 mm; range, 3-24 mm), and mean thickness was 5 mm (median, 4 mm; range, 1-20 mm). On the basis of individual chromosomal mutations, risk for metastasis was increased for chromosome 3 partial monosomy (hazard ratio [HR], 2.84; P = 0.001), 3 complete monosomy (HR, 6.7, P < 0.001), 6q loss (HR, 3.1, P = 0.003), 8p loss (HR, 21.5, P < 0.001), and 8q gain (HR, 9.8, P < 0.001). Kaplan-Meier estimate for melanoma-related metastasis in 1, 3, 5, and 7 years for 3 partial monosomy was 1%, 5%, 14%, and 17%; for 3 complete monosomy was 3%, 19%, 28%, and 37%; for 6q loss was 8%, 23%, 49%, and 49%; for 8p loss was 8%, 29%, not estimable (NE), and NE; and for 8q gain was 6%, 21%, 35%, 48%, respectively. On the basis of personalized cytogenetic profiles, Kaplan-Meier estimates (1, 3, and 5 years) for melanoma-related metastasis for 3, 6, and 8 disomy (1%, 1%, 4% [HR, 1]) were low compared with the higher-risk combinations of 3 complete monosomy, 6p gain, and 8q gain (0%, 29%, 29% [HR, 10.6, P = 0.02]); 3 complete monosomy, 6 disomy, 8q gain, and 8p gain (14%, 14%, NE [HR, 18.3, P = 0.02]); 3 complete monosomy, 6 disomy, and 8q gain (8%, 27%, 39% [HR, 19.5, P < 0.001]); and 3 complete monosomy, 6 disomy, 8q gain, and 8p loss (3%, 28%, NE [HR, 31.6, P < 0.001]), respectively. CONCLUSIONS:Risk for melanoma-related metastasis strongly correlates with personalized cytogenetic profiles, with 5-year Kaplan-Meier estimates ranging from 4% with chromosomes 3, 6, and 8 disomy up to 39% for 3 complete monosomy, 6 disomy, and 8q gain.

journal_name

Ophthalmology

journal_title

Ophthalmology

authors

Shields CL,Say EAT,Hasanreisoglu M,Saktanasate J,Lawson BM,Landy JE,Badami AU,Sivalingam MD,Hauschild AJ,House RJ,Daitch ZE,Mashayekhi A,Shields JA,Ganguly A

doi

10.1016/j.ophtha.2017.04.003

subject

Has Abstract

pub_date

2017-10-01 00:00:00

pages

1523-1531

issue

eissn

0161-6420

issn

1549-4713

pii

S0161-6420(17)30398-6

journal_volume

124

pub_type

杂志文章

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Personalized Prognosis of Uveal Melanoma Based on Cytogenetic Profile in 1059 Patients over an 8-Year Period: The 2017 Harry S. Gradle Lecture.