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

Autor:	Shields CL; Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: carolshields@gmail.com., Say EAT; Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania., Hasanreisoglu M; Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania., Saktanasate J; Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania., Lawson BM; Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania., Landy JE; Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania., Badami AU; Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania., Sivalingam MD; Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania., Mashayekhi A; Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania., Shields JA; Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania., Ganguly A; Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Jazyk:	angličtina
Zdroj:	Ophthalmology [Ophthalmology] 2017 May; Vol. 124 (5), pp. 609-618. Date of Electronic Publication: 2017 Jan 31.
DOI:	10.1016/j.ophtha.2016.12.026
Abstrakt:	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. (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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