Cytogenetic Abnormalities in Uveal Melanoma Based on Tumor Features and Size in 1059 Patients: The 2016 W. Richard Green Lecture.
To determine the risks for altered cytogenetic profile based on melanoma features and size.



Retrospective case series.



A total of 1059 patients with uveal melanoma.



Fine-needle aspiration biopsy (FNAB) of tumor for DNA amplification and whole genome array-based assay.



Risk for cytogenetic abnormalities based on features and size: small (≤3 mm thickness), medium (>3-<8 mm), and large (≥8 mm).



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).



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.
Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: carolshields@gmail.com.
Carol L
CL
Shields
Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.
Emil Anthony T
EAT
Say
Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.
Murat
M
Hasanreisoglu
Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.
Jarin
J
Saktanasate
Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.
Brendan M
BM
Lawson
Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.
Jeffrey E
JE
Landy
Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.
Anjali U
AU
Badami
Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.
Meera D
MD
Sivalingam
Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.
Arman
A
Mashayekhi
Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.
Jerry A
JA
Shields
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Arupa
A
Ganguly
D044963:Biopsy, Fine-Needle; D002869:Chromosome Aberrations; D002877:Chromosomes, Human; D002924:Ciliary Body / Q000473:pathology*; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods*; D012189:Retrospective Studies; D014604:Uveal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D000098943:Uveal Melanoma
D004273:DNA, Neoplasm