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JMD 2006, Vol. 8, No. 5
Copyright © 2006 American Society for Investigative Pathology & Association for Molecular Pathology

Prognostic Testing in Uveal Melanoma by Transcriptomic Profiling of Fine Needle Biopsy Specimens

Michael D. Onken^*, Lori A. Worley^*, Rosa M. Dávila, Devron H. Char and J. William Harbour^*

From the Departments of Ophthalmology & Visual Sciences * and Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri; and the Tumori Foundation, San Francisco, California

Many uveal melanoma patients die of metastasis despite ocular treatment. Transcriptomic profiling of enucleated tumors can identify patients at high metastatic risk. Because most uveal melanomas do not require enucleation, a biopsy would be required for this analysis. Here, we establish the feasibility of transcriptomic analysis of uveal melanomas from fine needle aspirates. Transcriptomic profiles were analyzed from postenucleation "mock" needle biopsies and matching tumors from eight enucleated eyes and from fine needle aspirates in 17 uveal melanomas before radiotherapy. Predictive accuracy was assessed using a weighted voting classifier optimized for probe set selection using a minimal redundancy/maximum relevance algorithm. Transcriptomic profiles from mock biopsies were highly similar to those from their matching tumor samples (P < 0.0001). Transcriptomic profiles from fine needle aspirates clustered into two classes with discriminating probe sets that overlapped significantly with those for our published classification (P < 0.00001). No loss of predictive accuracy was identified among eight needle aspirates obtained from a distant location. Thus, it is feasible to obtain RNA of adequate quality and quantity to perform transcriptomic analysis on uveal melanoma samples obtained by fine needle biopsy. This method can be applied to specimens obtained from distant geographic locations and can stratify uveal melanoma patients based on metastatic risk.

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