Purpose Most uveal melanoma patients (UMP) do not show evidence of metastases upon diagnosis. However, despite local tumour control, B50% 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 transcriptasepolymerase 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.

The aim of this study was to evaluate the immunohistochemical expression of phospho-Akt and its possible association with clinicopathological features in uveal melanoma. Thirty-four enucleated eyes from 34 patients with choroidal melanoma were included in the study. Patients were divided into two groups based on the treatment received: (1) primary enucleation (n=18); (2) radiotherapy, either external beam or brachytherapy, and enucleation (n=16). Clinicopathological data were obtained. The minimum follow-up time was 72 months. Immunohistochemistry for phospho-Akt was performed using an anti-phospho-Akt (Ser 473) rabbit antibody. The association of phospho-Akt with clinicopathological parameters was investigated in each patient group separately. Phospho-Akt immunostaining was cytoplasmic in both groups. In the primary enucleation group, 10 tumours were phospho-Akt positive (55.5%). Patients with phospho-Akt-positive tumours were older (average 70.8 years versus 59 years, P=0.01) and phospho-Akt immunoreactivity was significantly associated with a higher risk of metastatic disease (Kaplan-Meier analysis, P=0.02). In the radiotherapy and enucleation group, nine tumours were phospho-Akt positive (56.2%). The absence of phospho-Akt expression was correlated with male gender (P=0.02). The following conclusions can be drawn from this study: (1) phospho-Akt immunoexpression was detected in 55.5% of uveal melanomas treated with primary enucleation and in 56.2% of uveal melanomas treated with radiotherapy and enucleation; (2) the association of phospho-Akt immunoexpression with clinicopathological features, including prognosis, merits further study.

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