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Ophthalmology. 2017 Oct;124(10):1523-1531. doi: 10.1016/j.ophtha.2017.04.003. Epub 2017 May 7.

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

Author information

1
Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: carolshields@gmail.com.
2
Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.
3
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.

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.

PMID:
28495150
DOI:
10.1016/j.ophtha.2017.04.003
[Indexed for MEDLINE]

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