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.
"First proposed by Callender in 1931 and modified by McLean in 1983, the classification divides melanomas into spindle cell, epithelioid, and mixed cell type based on the morphology of the cells, their nuclei, and nucleoli.13,14 Epithelioid cell type is associated with a far worse prognosis because of higher rates of systemic metastases.15 "
[Show abstract][Hide abstract] ABSTRACT: Purpose
To describe a case of uveal melanoma in the peripheral choroid masquerading as chronic uveitis and to raise awareness about malignant masquerade syndromes.
A 36-year-old Chinese woman presented from an outside ophthalmologist with a 6-month history of unilateral chronic uveitis unresponsive to medical therapy in the left eye. She was found to have a uveal melanoma in the retinal periphery and underwent successful enucleation of her left eye. The histopathological diagnosis confirmed the clinical diagnosis.
When uveal melanoma presents in an atypical way, the diagnosis is more difficult. This case highlights the uncommon presentations of malignant melanoma of the choroid. It provides valuable information on how peripheral uveal melanoma can present with clinical signs consistent with an anterior uveitis.
Optometry and vision science: official publication of the American Academy of Optometry 07/2014; 91(9). DOI:10.1097/OPX.0000000000000350 · 1.60 Impact Factor
"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). "
[Show abstract][Hide abstract] 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.
Journal of Small Animal Practice 11/2013; 54(11):584-93. DOI:10.1111/jsap.12141 · 1.09 Impact Factor
[Show abstract][Hide abstract] 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.
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