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Cytogenetic Abnormalities in Uveal Melanoma Based on Tumor Features and Size in 1059 Patients: The 2016 W. Richard Green Lecture.

Abstract：

PURPOSE:To determine the risks for altered cytogenetic profile based on melanoma features and size. DESIGN:Retrospective case series. PARTICIPANTS:A total of 1059 patients with uveal melanoma. METHODS:Fine-needle aspiration biopsy (FNAB) of tumor for DNA amplification and whole genome array-based assay. MAIN OUTCOME MEASURES:Risk for cytogenetic abnormalities based on features and size: small (≤3 mm thickness), medium (>3-<8 mm), and large (≥8 mm). RESULTS:Of 1059 patients with uveal melanoma sampled for status of chromosomes 3, 6, and 8, comparison (normal [disomy] chromosomes 3, 6, and 8 vs. any 3, 6, or 8 abnormality) revealed differences in mean age (55 vs. 58 years, P = 0.018), ocular melanocytosis (1% vs. 5%, P = 0.027), mean visual acuity (VA) (20/30 vs. 20/50, P = 0.011), poor VA (≤20/200) (9% vs. 15%, P = 0.041), ciliary body location (5% vs. 11%, P < 0.001), extramacular location (73% vs. 87%, P < 0.001), increased mean distance to optic disc (3.3 vs. 5.0 mm, P < 0.001) and foveola (3.1 vs. 4.7 mm, P < 0.001), and increased mean basal diameter (9.8 vs. 12.6 mm, P < 0.001) and thickness (3.8 vs. 5.9 mm, P < 0.001). Tumors classified as small, medium, and large showed abnormalities with loss of disomy of chromosomes 3 (35%/52%/65%), 6 (15%/34%/51%), and 8 (19%/41%/69%), respectively. By comparison (medium/large vs. small melanoma), the odds ratio (OR) included complete monosomy 3 (3.09, P < 0.001), partial monosomy 3 (1.44, P = 0.053), 6p gain (3.78, P < 0.001), 6q gain (1.37, P = 0.537), 6p loss (2.52, P = 0.410), 6q loss (12.61, P < 0.001), 8p gain (6.16, P < 0.001), 8p loss (6.04, P < 0.001), and 8q gain (4.87, P < 0.001). For chromosome 3 monosomy, the OR was highest for ciliary body location (8.17, P < 0.001), tumor thickness ≥8 mm (2.70, P < 0.001), tumor base ≥10 mm (2.59, P < 0.001), and age ≥60 years (1.83, P < 0.001). For chromosome 8p loss, the OR was highest for ciliary body location (53.91, P = 0.008), ocular melanocytosis (3.95, P = 0.038), and thickness ≥8 mm (5.14, P < 0.001), whereas for 8q gain, the OR was highest for ciliary body location (102.87, P = 0.001), thickness >8 mm (4.44, P < 0.001), and ocular melanocytosis (2.75, P = 0.049). CONCLUSIONS:Increasing melanoma size demonstrates greater cytogenetic alterations. Alterations in chromosome 8 show unique correlation with melanocytosis. This suggests that prompt management of small melanoma might reduce chromosomal instability and could improve overall patient survival.

journal_name

Ophthalmology

journal_title

Ophthalmology

authors

Shields CL,Say EAT,Hasanreisoglu M,Saktanasate J,Lawson BM,Landy JE,Badami AU,Sivalingam MD,Mashayekhi A,Shields JA,Ganguly A

doi

10.1016/j.ophtha.2016.12.026

subject

Has Abstract

pub_date

2017-05-01 00:00:00

pages

609-618

issue

eissn

0161-6420

issn

1549-4713

pii

S0161-6420(16)31846-2

journal_volume

124

pub_type

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Cytogenetic Abnormalities in Uveal Melanoma Based on Tumor Features and Size in 1059 Patients: The 2016 W. Richard Green Lecture.