Bertil Damato1, Sarah E Coupland. 1. Liverpool Ocular Oncology Centre, St. Paul's Eye Clinic, Royal Liverpool University Hospital, Liverpool, England. bertil@damato.co.uk
Abstract
OBJECTIVE: To report our experience in translating uveal melanoma cytogenetics to routine clinical practice. METHODS: In 1998, we confirmed that monosomy 3 in uveal melanomas correlates with mortality. In 1999, we started offering all patients treated by enucleation or local resection the possibility of monosomy 3 testing, using fluorescence in situ hybridization. In 2006, we started analyzing tumors with multiplex ligation-dependent probe amplification, which provided more information from smaller samples. In 2007, we extended this service to patients undergoing radiotherapy or phototherapy. RESULTS: Initial expectations regarding the sensitivity and specificity of monosomy 3 tests in predicting metastatic death were found to be overoptimistic. Cytogenetic classification of uveal melanomas into "lethal" and "nonlethal" types was insufficient for estimating risk of metastasis. Prognostication also required consideration of (1) clinical tumor stage; (2) histologic grading of malignancy; and (3) influence of age and sex on life expectancy. We developed a neural network for such multivariate analysis. Metastatic deaths occurred without monosomy 3, possibly because small deletions were missed or because of tumor heterogeneity. CONCLUSION: Genomic typing of uveal melanomas proved more complex than we had anticipated but enabled us to reassure patients with a good prognosis while targeting systemic screening at high-risk cases.
OBJECTIVE: To report our experience in translating uveal melanoma cytogenetics to routine clinical practice. METHODS: In 1998, we confirmed that monosomy 3 in uveal melanomas correlates with mortality. In 1999, we started offering all patients treated by enucleation or local resection the possibility of monosomy 3 testing, using fluorescence in situ hybridization. In 2006, we started analyzing tumors with multiplex ligation-dependent probe amplification, which provided more information from smaller samples. In 2007, we extended this service to patients undergoing radiotherapy or phototherapy. RESULTS: Initial expectations regarding the sensitivity and specificity of monosomy 3 tests in predicting metastatic death were found to be overoptimistic. Cytogenetic classification of uveal melanomas into "lethal" and "nonlethal" types was insufficient for estimating risk of metastasis. Prognostication also required consideration of (1) clinical tumor stage; (2) histologic grading of malignancy; and (3) influence of age and sex on life expectancy. We developed a neural network for such multivariate analysis. Metastatic deaths occurred without monosomy 3, possibly because small deletions were missed or because of tumor heterogeneity. CONCLUSION: Genomic typing of uveal melanomas proved more complex than we had anticipated but enabled us to reassure patients with a good prognosis while targeting systemic screening at high-risk cases.
Authors: Mohamed H Abdel-Rahman; Benjamin N Christopher; Mohammed F Faramawi; Khaled Said-Ahmed; Carol Cole; Andrew McFaddin; Abhik Ray-Chaudhury; Nyla Heerema; Frederick H Davidorf Journal: Mod Pathol Date: 2011-04-15 Impact factor: 7.842
Authors: Benjamin N Christopher; Colleen M Cebulla; Paul E Wakely; Frederick H Davidorf; Mohamed H Abdel-Rahman Journal: Exp Eye Res Date: 2011-09-17 Impact factor: 3.467
Authors: T Huibertus van Essen; Sake I van Pelt; Mieke Versluis; Inge H G Bronkhorst; Sjoerd G van Duinen; Marina Marinkovic; Wilma G M Kroes; Claudia A L Ruivenkamp; Shruti Shukla; Annelies de Klein; Emine Kiliç; J William Harbour; Gregorius P M Luyten; Pieter A van der Velden; Rob M Verdijk; Martine J Jager Journal: Br J Ophthalmol Date: 2014-08-21 Impact factor: 4.638
Authors: Andrea Russo; Sarah Ellen Coupland; Michael O'Keefe; Bertil E Damato Journal: Graefes Arch Clin Exp Ophthalmol Date: 2010-02-09 Impact factor: 3.117
Authors: Mohamed H Abdel-Rahman; Colleen M Cebulla; Vishal Verma; Benjamin N Christopher; William E Carson; Thomas Olencki; Frederick H Davidorf Journal: Exp Eye Res Date: 2012-05-05 Impact factor: 3.467