Uveal melanoma prognostication: from lesion size and cell type to molecular class

Division of Oculofacial Plastic and Orbital Surgery, University of California, San Francisco, CA 94115, USA.
Canadian Journal of Ophthalmology (Impact Factor: 1.3). 06/2012; 47(3):246-53. DOI: 10.1016/j.jcjo.2012.03.038
Source: PubMed

ABSTRACT To review the evidence for molecular genetic testing of uveal melanoma in the context of prognostic indicators of metastasis and tumour-related mortality.
Review of the literature and personal experiences of the authors.
We conducted a MEDLINE, Embase, and PubMed literature search (1980-2011) for English-language abstracts and full-text references regarding molecular genetic testing of uveal melanoma. Search terms included uveal, melanoma, cytogenetic, gene, and molecular. All studies in which patients with primary uveal melanoma underwent molecular genetic testing with survival data for disease-related metastasis and mortality were reviewed.
From 176 identified articles, 40 were scientific studies of uveal melanomas that included histologic and molecular genetic analysis. Of those, 24 included survival data, correlation of molecular genetic features with other prognostic indicators, or both. Cytogenetic and microarray gene expression analysis allows uveal melanoma lesions to be classified as high risk or low risk for metastasis and disease-related mortality. Gene expression profiling supersedes clinical, histologic, and cytogenetic prognosticators.
Uveal melanoma comprises a heterogeneous group of malignancies based on its molecular biology. Molecular class by gene expression profiling has the most strongly predictive value for uveal melanoma metastasis and mortality.

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    • "Once there is evidence of metastatic disease death usually occurs within 7 months (Gamel et al. 1993). Although poor survival has been correlated with advanced patient age, anterior tumour location, increased tumour size, epithelioid cell type and tumoural scleral invasion, they are inaccurate at predicting metastasis in an individual patient (Prescher et al. 1996, Scholes et al. 2003, Worley et al. 2007, Gill et al. 2012). Cytogenetic analysis has identified a number of unbalanced genomic aberrations associated with patient outcome (Prescher et al. 1996, Sisley et al. 1997, Kilic et al. 2005, van Gils et al. 2008). "
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    ABSTRACT: To evaluate if 14 genes that discriminate metastasising and non-metastasising human uveal melanomas can differentiate metastasising and non-metastasising uveal melanomas in dogs. Nineteen archival biopsies of eyes with a histopathological classification of primary benign (n = 9) and malignant (n = 10) uveal melanoma were selected. Thoracic and/or abdominal metastases confirmed metastatic spread of the primary tumour in seven dogs during the follow-up period. Gene expression was assayed by Reverse Transcription-quantitative Polymerase Chain Reaction. Genes displaying statistically significant differences in expression between the metastasising and non-metastasising tumours were identified. Four genes (HTR2B, FXR1, LTA4H and CDH1) demonstrated increased expression in the metastasising uveal melanomas. This preliminary study illustrates the potential utility of gene expression markers for predicting canine uveal melanoma metastasis. The genes displaying elevated expression in the metastasising tumours are part of a 12-discriminating gene set used in a routine assay, performed on fine needle aspirate biopsies collected without enucleation, for predicting human uveal melanoma metastasis. Further work is required to validate the results.
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    ABSTRACT: Uveal melanoma is the most common malignant tumour of the adult eye. Around half of all uveal melanoma patients will eventually die of their disease. There are a number of effective options to treat the primary tumour locally, but once the tumour has metastasised, there are no curative therapies. Traditionally, the diagnosis of uveal melanoma and prognostic prediction was based solely on the clinical presentation and detailed histopathological evaluation. Recent genetic findings have shed light on the biology of these tumours, and led to the development of genetic tests that can help assess their malignant potential and prognosis. The genes, proteins and pathways that have been (and continue to be) discovered will likely result in novel targeted therapeutic approaches with high efficacy and low toxicity. In this review, we summarise the clinical, pathological and genetic features of uveal melanoma, with emphasis on recent discoveries.
    Pathology 12/2012; DOI:10.1097/PAT.0b013e32835c6505 · 2.62 Impact Factor
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    ABSTRACT: Uveal melanoma (UM) is the most common cause of primary eye cancer in the western world. During embryogenesis neural crest cells migrate to the neural tract where they develop into melanocytes. Melanomas of the uvea are derived from these melanocytes. UM may arise in the iris (5%), ciliary body (23%) or choroid (72%). Choroidal melanomas are the most common and usually display a discoid, dome-shaped or mushroom shaped growth pattern. Approximately 80% of the primary intraocular tumours are diagnosed as UM in patients above the age of 20 years, with a mean age of 60 years (Singh & Topham, 2003). Despite a shift towards more conservative eye treatments, survival has not improved during 1973 to 2008 (Singh et al, 2011). Growth of the primary tumour is related with histopathological features, as well as the genetic changes within these tumours. In this chapter we will not discuss iris melanoma, as this shows a different clinical and genetic behaviour, compared to ciliary body and choroidal melanoma. The clinical features, histopathological profile and genetic alterations of UM, as well as therapeutic options for primary tumours and metastases will be discussed.
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