Cytogenetics of Uveal Melanoma: A 7-Year Clinical Experience
Presented at: Research and Development Open Day, October 2006, Liverpool, United Kingdom; Wills Eye Hospital departmental lecture, November 2006, Philadelphia, Pennsylvania; Nijmegen Hospital departmental lecture, December 2006, Nijmegen, Netherlands; Danish Ophthalmological Society meeting, November 2006, Copenhagen, Denmark; and International Congress of Ocular Oncology, June 2007, Siena, Italy.
Received 8 January 2007; received in revised form 3 June 2007; accepted 5 June 2007. published online 28 August 2007.
Purpose
Chromosome 3 loss and chromosome 8 gains in uveal melanoma are associated with metastatic death. Since 1999, we have offered cytogenetic analysis to patients treated by local resection or enucleation. This study correlated our cytogenetic results with clinical and histologic predictors and disease-specific mortality.
Design
Nonrandomized case series.
Participants
Three hundred fifty-six patients with uveal melanoma with data on chromosome 3 and chromosome 8.
Methods
Tumor diameter was measured by echography. Cell type, presence of closed connective tissue loops, and mitotic rate were determined histopathologically. Fluorescence in-situ hybridization was performed using centromeric probes for chromosomes 3 and 8 and for c-myc. Patients were flagged at the National Health Service Cancer Registry, which notified us of any deaths. Statistics included Cox multivariate analysis and Kaplan–Meier analysis.
Main Outcome Measures
Disease-specific mortality, according to clinical, histologic and cytogenetic features as well as correlation between cytogenetic variables and other mortality predictors, including a predictive index.
Results
The patients had a mean age of 61.9 years. The tumors showed no cytogenetic abnormalities of chromosomes 3 or 8 in 42%, chromosome 8 gains in 11%, monosomy 3 in 21%, and both abnormalities in 27%. These correlated with ciliary body involvement (P<0.001), extraocular spread (P = 0.007), large basal tumor diameter (P<0.001), epithelioid cellularity (P<0.001), closed connective tissue loops (P<0.001), and mitotic rate exceeding 4/40 high power fields (P<0.001). By the study close, 76 patients had died (67 from metastasis). Cox multivariate analysis showed the most significant factors to be basal tumor diameter (P<0.001), monosomy 3 (P<0.001), and epithelioid cellularity (P = 0.004). A predictive index (PI) was derived from these variables. Kaplan–Meier analysis showed that 5-year metastatic death rates ranged from 0% in 84 patients with low-grade melanoma (PI<19) to 66% in 100 patients with high-grade tumor (PI>26; 95% confidence interval, 53%–80%).
Conclusion
Cytogenetic analysis of chromosomes 3 and 8 enhances prediction of disease-specific mortality after treatment of uveal melanoma but must be interpreted together with tumor diameter and cell type.
1Ocular Oncology Service, Royal Liverpool University Hospital, Liverpool, United Kingdom.
2Regional Cytogenetics Laboratory, Liverpool Womens Hospital, Liverpool, United Kingdom.
3Department of Pathology, Royal Liverpool University Hospital, Liverpool, United Kingdom.
4Unit of Ophthalmology, School of Clinical Sciences, University of Liverpool, Liverpool, United Kingdom.
5IC Statistical Services, West Kirby, United Kingdom.
Correspondence to Bertil Damato, MD, PhD, Ocular Oncology Service, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, UK.
Manuscript no. 2007-29.
Supported by the Eye Tumour Research Fund of the Royal Liverpool University Hospital. The Ocular Oncology Service in Liverpool and the cytogenetic studies were funded by the National Specialist Commissioning Advisory Group of the National Health Service Department of Health, London, United Kingdom.
The authors have no commercial or proprietary interest in the products or companies mentioned in the article.
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