Microarray classification outperforms known prognostic indicators for UM, such as clinical, histopathologic, and cytogenetic parameters. In addition, the identified regions with lower expressed genes on 3p could harbor genes that are responsible for the poor prognosis of patients with UM.

Although a small number of uveal melanomas show heterogeneity for chromosome 3, it does not affect survival. In the presence of triploid clones, the loss of chromosome 3 is more difficult to interpret. In general, tumor biopsies in uveal melanoma provide an accurate prediction of the patient's prognosis.

Uveal melanoma (UM) is the most frequently found primary intra-ocular tumor in adults. It is a highly aggressive cancer that causes metastasis-related mortality in up to half of the patients. Many independent studies have reported somatic genetic changes associated with high metastatic risk, such as monosomy of chromosome 3 and mutations in BAP1. Still, the mechanisms that drive metastatic spread are largely unknown. This study aimed to elucidate the potential role of microRNAs in the metastasis of UM. Using a next-generation sequencing approach in 26 UM samples we identified thirteen differentially expressed microRNAs between high-risk UM and low/intermediate-risk UM, including the known oncomirs microRNA-17-5p, microRNA-21-5p, and miR-151a-3p. Integration of the differentially expressed microRNAs with expression data of predicted target genes revealed 106 genes likely to be affected by aberrant microRNA expression. These genes were involved in pathways such as cell cycle regulation, EGF signaling and EIF2 signaling. Our findings demonstrate that aberrant microRNA expression in UM may affect the expression of genes in a variety of cancer-related pathways. This implies that some microRNAs can be responsible for UM metastasis and are promising potential targets for future treatment.

Dendritic cell vaccination is feasible and safe in metastatic uveal melanoma. Dendritic cell-based immunotherapy is potent to enhance the host's antitumor immunity against uveal melanoma in approximately one third of patients. Compared with other prospective studies with similar inclusion criteria, dendritic cell vaccination may be associated with longer than average overall survival in patients with metastatic uveal melanoma.

Mutations that are often found in uveal and cutaneous melanoma were identified in this cohort of iris melanomas and iris nevi. Therefore, iris melanomas harbor a molecular profile comparable to both choroidal melanoma and cutaneous melanoma. These findings may offer adjuvant targeted therapies for iris melanoma. There was no prognostic significance of BAP1 expression as seen in choroidal melanoma. Consequently, iris melanoma is a distinct molecular subgroup of UM. Histologic borderline malignant iris nevi can harbor BAP1 mutations and may be designated iris melanocytic tumors of uncertain malignant potential.

In uveal melanoma, loss of chromosome 3 and gain of chromosome 8q are associated with a high risk of metastasis. In this study, we validated the use of multiplex ligation-dependent probe amplification (MLPA) in detecting patients at risk for metastatic disease in comparison with the predictive power of fluorescence in-situ hybridization (FISH). For 64 uveal melanoma samples, the MLPA results of chromosome 3 and 8 were compared with the results obtained by FISH. For seven samples, a single nucleotide polymorphism array was performed to clarify discrepancies. Clinical information together with the histopathology and chromosomal aberrations of chromosomes 1, 3, 6, and 8 were evaluated for correlation with the patients' prognosis. Loss of chromosome 3, loss or gain of 8p, and gain of 8q, found with MLPA, correlated with a significantly lower disease-free survival (P<0.001). On the basis of the clinical outcome, 12 patients would have been classified incorrectly using MLPA results of chromosomes 3 and 8. FISH results led to the same incorrect classification. Four patients with abnormalities of chromosomes 3 and 8 in the tumor, detected with MLPA, are still alive without metastasis. Eight patients without concurrent aberrations of chromosomes 3 and 8 in the tumors died due to metastasis. The sensitivity of MLPA to detect patients at risk for metastatic disease is higher than with the results obtained with FISH (0.795 vs. 0.692). The specificity is equal for both techniques (0.840). MLPA is able to detect patients at risk for metastasis using the results for chromosomes 3 and 8. There is no significant difference in the predictive power of MLPA compared with FISH.

Ocular melanoma consists of posterior uveal melanoma, iris melanoma and conjunctival melanoma. These malignancies derive from melanocytes in the uveal tract or conjunctiva. The genetic profiles of these different entities differ from each other. In uveal melanoma, GNAQ and GNA11 gene mutations are frequently found and prognosis is based on mutation status of BAP1, SF3B1 and EIF1AX genes. Iris melanoma, also originating from the uvea, has similarities to the genetic makeups of both posterior uveal melanoma (UM) and conjunctival melanoma since mutations in GNAQ and GNA11 are less common and genes involved in conjunctival melanoma such as BRAF have been described. The genetic spectrum of conjunctival melanoma, however, includes frequent mutations in the BRAF, NRAS and TERT promoter genes, which are found in cutaneous melanoma as well. The BRAF status of the tumor is not correlated to prognosis, whereas the TERT promoter gene mutations are. Clinical presentation, histopathological characteristics and copy number alterations are associated with survival in ocular melanoma. Tissue material is needed to classify ocular melanoma in the different subgroups, which creates a need for the use of noninvasive techniques to prognosticate patients who underwent eye preserving treatment.

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