ABSTRACT
PURPOSE: Monosomy 3 (M3) and abnormalities of chromosome 8 associate with poor prognosis in uveal melanomas (UM). Although M3 has been the subject of more in-depth studies, none have intensively focused on chromosome 8. To elucidate the potential role of chromosome 8 abnormalities, array comparative genomic hybridization (aCGH) was performed on primary UM. METHODS: A specifically-designed custom high-resolution array was developed focusing on changes most implicated in UM. Probes for chromosome 8 had a mean spacing of 2.3 kb while chromosomes infrequently affected had a mean spacing of 36.6 kb. A series of 75 UM, including one formalin-fixed paraffin sample were analyzed, and where possible control DNA extracted from the patient's own peripheral blood was used. RESULTS: The most common copy number abnormalities were chromosome 8 (75%) and M3 (51%), with M3 and gain of the long arm of chromosome 8 (8q+) associated in 41% of cases. Also identified were partial deletions of chromosome 3 (3%) and regional 8q+ (23%), and the intensive coverage of chromosome 8 revealed small focal deletions and amplifications affecting both arms. The most significant predictor of prognosis was M3/8q+ having a hazard ratio of 10.1 (P < 0.0001). CONCLUSIONS: Neither 8p deletion nor focal changes affecting chromosome 8 were linked to outcome. The most significant indicator was M3/8q, and multiple 8q+ associated with shorter survival. Studying UM with this technology provides a powerful robust tool for predicting prognosis while considering other genetic changes, allowing the future incorporation of such data as it becomes clinically significant.
Subject(s)
Chromosomes, Human, Pair 8/genetics , Comparative Genomic Hybridization/methods , Gene Amplification , Genetic Predisposition to Disease/genetics , Melanoma/genetics , Sequence Deletion , Uveal Neoplasms/genetics , Adult , Aged , Aged, 80 and over , DNA Copy Number Variations , Female , Humans , Male , Microarray Analysis/methods , Middle Aged , Monosomy/genetics , Regression Analysis , Survival Analysis , Young AdultSubject(s)
Choroid Neoplasms/pathology , Melanoma/pathology , Nevus, Pigmented/pathology , Aged , Choroid Neoplasms/blood supply , Coloring Agents , Female , Fluorescein Angiography , Humans , Indocyanine Green , Male , Melanoma/blood supply , Middle Aged , Nevus, Pigmented/blood supply , Ophthalmoscopy , Retrospective StudiesABSTRACT
PURPOSE: To evaluate clinical features at presentation of small choroidal melanocytic lesions that were predictive of growth. DESIGN: Retrospective observational case series. PARTICIPANTS: A cohort of 240 patients with a presumptive diagnosis of small choroidal melanocytic lesions who were observed to document growth before treatment. METHODS: Data regarding size, location, diagnostic features, and growth were collected. To evaluate the diagnostic features at presentation, Barnard and Fisher exact tests were performed for categorical variables, and the Wilcoxon rank sum test was used for continuous factors. MAIN OUTCOME MEASURE: Documented growth. RESULTS: Eleven patients with small choroidal melanocytic lesions (4.6%) demonstrated growth within 50 months of follow-up. Lesions that demonstrated growth were significantly thicker (> or =2.0 mm; P<0.001) and closer to the foveola (<3.0 mm; P = 0.002). Significant increases in the risk of growth also were observed for gender (male), presence of symptoms, and orange pigment. CONCLUSIONS: Significant clinical features of small choroidal melanocytic lesions predictive of growth are greater thickness (> or =2.0 mm), location closer to the foveola (<3.0 mm), and presence of symptoms and orange pigment.
