Clinical Study
Eye (2007) 21, 752–759; doi:10.1038/sj.eye.6702322; published online 31 March 2006
Identification of circulating malignant cells and its correlation with prognostic factors and treatment in uveal melanoma. A prospective longitudinal study
Part of this work was previously presented as a poster at ARVO 2005
S A Callejo1, E Antecka1, P L Blanco1, C Edelstein2 and M N Burnier Jr1
- 1The Henry C Witelson Ophthalmic Pathology Laboratory and Registry, McGill University Health Center, Montreal, Quebec, Canada
- 2Department of Ophthalmology, McGill University Health Care Center, Montreal, Quebec, Canada
Correspondence: MN Burnier, The Henry C Witelson Ophthalmic Pathology Laboratory, Lyman Duff Building, 3775 Rue University #216A, Montreal, Quebec, Canada H3A 2B4 Tel: +1 514 398 7192 ext 00384; Fax: +1 514 398 5728. E-mail: miguel.burnier@mcgill.ca
Received 8 June 2005; Accepted 29 January 2006; Published online 31 March 2006.
Abstract
Purpose
Most uveal melanoma patients (UMP) do not show evidence of metastases upon diagnosis. However, despite local tumour control, 
50% of them will develop metastases. These findings suggest that malignant cells may have already disseminated by the time of initial diagnosis. The purpose of the study was to detect circulating malignant cells (CMCs) in UMP and to correlate them with prognostic factors and therapy.
Methods
Nested reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect CMCs. In each UMP, blood was collected every 3 months. In each visit, 20 RT-PCR tests were performed. The date of diagnosis, largest tumour dimension, type, and date of treatment were obtained.
Results
A total of 30 UMP were enrolled. Five patients were enrolled at the time of diagnosis and 25 patients between 1 and 17 years following diagnosis. No UMP showed clinical evidence of metastasis. A total of 136 visits were registered, 1360 samples collected, and 2720 RT-PCRs performed. CMCs were identified in 29 patients in 119 visits (87.5%). However, in each visit, a low number of positive tests were recorded. CMCs were found in newly diagnosed, irradiated, enucleated, and observed patients regardless of tumour size and time period following treatment.
Conclusions
Uveal melanoma (UM) is not a localized ocular disease. CMCs were recorded at initial diagnosis confirming the early metastatic nature of UM. CMCs were present following treatment, including enucleation, demonstrating that CMCs are capable of disseminating and surviving, possibly as micrometastasis, which would contribute to the pool of CMCs at a later stage. Systemic therapy should be evaluated.
Keywords:
uveal melanoma, metastatic uveal melanoma, circulating malignant cells, micrometastasis, RT-PCR, minimal residual disease
