April 2016, Vol. 5, No. 3

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Biomarker for Uveal Melanoma Has Immediate Clinical Impact


Biomarker for Uveal Melanoma Has Immediate Clinical ImpactA new biomarker can identify the subgroup of Class 1 uveal melanomas most likely to metastasize, according to a retrospective study published in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR). Among Class 1 uveal melanomas, those with high levels of PRAME mRNA were more likely to metastasize than those with low levels of PRAME mRNA.

“We were surprised to find that 1 biomarker-PRAME-was sufficient to identify the subgroup of Class 1 uveal melanomas with increased metastatic risk. These findings could have immediate clinical impact. The data imply that patients with Class 1 uveal melanomas with increased PRAME expression should be managed differently than patients with Class 1 uveal melanomas without PRAME expression. They should be monitored more closely for metastatic disease and should be considered for clinical trials of adjuvant therapy,” stated lead author J. William Harbour, MD, Director of the Bascom Palmer Eye Institute at the University of Miami Miller School of Medicine, FL, in a news release from AACR.

As background, each year in the United States, an estimated 2000 to 3000 cases of uveal melanoma are diagnosed. These tumors are classified as Class 1 or 2 by gene expression profile. Class 1 uveal tumors have a much lower chance of metastasizing than Class 2, but about 10% of Class 1 tumors do metastasize.

The authors performed genome-wide analysis of mRNA isolated from 5 Class 1 uveal melanomas that metastasized and 8 Class 1 tumors that did not metastasize. PRAME was the most highly overexpressed mRNA in the tumors that metastasized. In an analysis of additional samples using quantitative polymerase chain reaction (PCR), the researchers found that 7 of 8 tumors that metastasized had high levels of PRAME mRNA and that 16 of 19 Class 1 tumors that did not metastasize had minimal levels of PRAME mRNA.

Next, they studied 64 Class 1 uveal melanoma samples using quantitative PCR and found that 39 (61%) had low levels of PRAME mRNA (PRAME negative) and 25 (39%) had high levels of PRAME mRNA (PRAME positive). No PRAME-negative tumor metastasized, while 7 of the 25 PRAME-positive tumors metastasized. The estimated 5-year rate of metastasis was 0% for PRAME-negative tumors and 38% for PRAME-positive tumors.

These findings were validated in 2 additional data sets, and both analyses showed that PRAME-positive uveal melanomas were significantly more likely to metastasize compared with PRAME-negative tumors.

A prospective multicenter trial is now being planned using this biomarker to determine risk of metastasis in Class 1 uveal melanomas.

Thus far, Class 1 and 2 gene expression profile test is the only prognostic assay for uveal melanoma to be prospectively validated in a multicenter study.

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