domingo, 6 de noviembre de 2011

Gene Expression Reveals Metastatic Risk in Uveal Melanoma

From Medscape Medical News

Gene Expression Reveals Metastatic Risk in Uveal Melanoma

Brian Hoyle

October 31, 2011 (Orlando, Florida) — A study evaluating the DecisionDx-UM (Castle Biosciences) test for metastatic uveal melanoma has revealed an overall predictive success rate approaching 100%, confirming the test's value in identifying those most at risk for metastasis.

The results of the multi-institute study were presented by Chris Bergstrom, MD, from the Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, here at American Academy of Ophthalmology 2011 Annual Meeting.

The "successful class assignment in 97% of patient samples received from over 60 physicians throughout the United States is a significantly higher success rate, compared with single-center monosomy of chromosome 3 and other pathological prognostic factors available to uveal melanoma patients," Dr. Bergstrom and the other researchers conclude in their poster.

Uveal melanoma is relatively rare; it is diagnosed in only about 7 people per million annually in the United States. Still, the disease is the most common eye cancer in adults. Furthermore, if present, the inherent chemo and radiation resistance can, with the class 2 version of the tumor, make the cancer prone to spread to organs, including the liver, where the disease can quickly become life-threatening.

In the study, 62 physicians acquired fine-needle aspirate biopsy tissue samples from 806 patients with uveal melanoma. The biopsy tissue was shipped directly or fixed and sectioned onto slides and then shipped to a central laboratory. Complementary DNA was synthesized from RNA extracted from each sample, and was used in a reverse-transcription polymerase chain reaction procedure to probe for the expression of 12 target genes that have been implicated in class 1A (low metastatic risk), class 1B (intermediate metastatic risk), and class 2 (high metastatic risk) uveal melanoma. The use of control genes validated the test procedure.

After excluding the results from 36 samples (3%) that contained too little or too much fluid, had been improperly fixed, or were improperly shipped, a success rate for proper class assignment of 97% was evident.

Class 1A was reported in 45% of the cases, class 1B in 18% of cases, and class 2 in 37% of cases. These proportions closely match validation sets for the same test that have been previously published. Ongoing assessment of the class assignments with the real-world outcome of tumor behavior has shown 100% agreement.

The results indicate that, as long as the sample fixation and/or shipping are suitable, the testing outcome is accurate. This enables the discrimination of low-priority tumors from those with a greater risk for metastasis.

"Ocular melanoma has a strong propensity to spread to the liver. When it does, it usually leads to death in a very short time. The information gained from the genetic signatures in ocular melanomas may one day help to predict which of the [tiny pigmented tumors] will turn into melanomas, allowing them to be treated earlier to reduce the chance of metastasis," said William Harbour, MD, from the Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri.

The study was funded by Castle Biosciences. Dr. Bergstrom and Dr. Harbor have disclosed no relevant financial relationships.

American Academy of Ophthalmology (AAO) 2011 Annual Meeting: Abstract PO425. Presented on October 31, 2011.
Gene Expression Reveals Metastatic Risk in Uveal Melanoma

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