A new biomarker can identify the subgroup of class 1 uveal melanomas that are most likely to metastasize, according to a new retrospective study (Field MG, et al. Clin Cancer Res. 2016;22:1234-1242). Among class 1 uveal melanomas, those with high levels of PRAME messenger RNA (mRNA) were more likely to metastasize than those with low levels of PRAME mRNA.
“We were surprised to find that one biomarker alone—PRAME—was sufficient to identify the subgroup of class 1 tumors with increased metastatic risk. These findings could have immediate clinical impact,” stated lead investigator J. William Harbour, MD, Director of Ocular Oncology, Bascom Palmer Eye Institute, University of Miami Health System, Florida, in a press release. “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 they should be considered for clinical trials of adjuvant therapy.”
As background, an estimated 2000 to 3000 cases of uveal melanoma are diagnosed annually in the United States. These tumors are classified as class 1 or class 2 by gene-expression profiling. Class 1 uveal tumors have a much lower chance of metastasizing than class 2, but approximately 10% of class 1 tumors metastasize.
The investigators performed a genome-wide analysis of mRNA that was isolated from 5 class 1 uveal melanomas that had metastasized and 8 class 1 tumors that had not. PRAME was the most highly overexpressed mRNA in the tumors that had metastasized. In an analysis of additional samples using quantitative polymerase chain reaction (PCR), 7 of 8 tumors that had metastasized had high levels of PRAME mRNA, and 16 of 19 class 1 tumors that had not metastasized had minimal levels of PRAME mRNA.
None of the PRAME-negative tumors metastasized, whereas 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, which showed that PRAME-positive uveal melanomas were significantly more likely to metastasize than PRAME-negative tumors.
Thus far, class 1 and class 2 gene-expression testing is the only prognostic assay for uveal melanoma to be prospectively validated in a multicenter study.
