A new biomarker measurement might improve the accuracy of prognostic testing and precision medicine in uveal melanoma, according to a study published in Clinical Cancer Research.1
Higher rates of metastasis in patients with class 1 uveal melanoma were correlated with the presence of the mRNA biomarker known as PRAME, or preferentially expressed antigen in melanoma. These findings suggested that patients with the PRAME biomarker should be monitored more closely.
This study assessed whether any biomarkers are associated with class 1 uveal melanoma metastasis. Typically, class 1 uveal melanoma has a lower risk of metastatic disease. Gene expression profiling can distinguish between class 1 and class 2 uveal melanoma. Patients with class 1 uveal melanoma continue, nonetheless, to have a risk of developing metastatic disease.
“About 10% of patients with class 1 uveal melanoma do develop metastasis. The main purpose of this study was to identify a clinically useful biomarker for this subgroup of class 1 uveal melanomas, which in turn might help in the development of precision medicines for melanoma patients,” said J. William Harbour, MD, associate director for Basic Research and leader of the Eye Cancer Site Disease Group at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, Miami, Florida.
This study examined data and tumor samples from 389 patients whose uveal melanoma were designated as class 1 or class 2 based on a 12-gene prognostic classifier. PRAME mRNA expression was examined in 64 class 1 tumors via quantitative PCR.
In patients with class 1 uveal melanoma, PRAME mRNA expression was predictive of metastasis (P=.0006). At 5 years, no patients in the PRAME-negative class 1 uveal melanoma group developed metastatic disease, whereas 38% of the PRAME-positive class 1 uveal melanoma group did develop metastatic disease. In patients with class 2 disease, 71% developed metastatic disease.
Expression of PRAME correlated with SF3B1 mutations (P=.003) and larger tumor diameter (P=.05). Class 1 PRAME-positive patients had a median metastasis-free survival of 88 months, and class 2 patients had a median metastasis-free survival of 32 months.
“We were surprised to find that one biomarker alone, PRAME, was sufficient to identify the subgroup of class 1 tumors with increased metastatic risk,” stated Harbour.
“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 they should be considered for clinical trials of adjuvant therapy.”
As this was a retrospective study, the researchers are planning a prospective study to follow up on the findings.
1. Field MG, Decatur CL, Kurtenbach S, et al. PRAME as an independent biomarker for metastasis in uveal melanoma. Clin Cancer Res. 2016:22(5):1234-1242. doi:10.1158/1078-0432.CCR-15-2071.