Biomarker Identifies Uveal Melanoma Patients at Risk for Metastasis

Uveal melanoma is a cancer (melanoma) of the eye involving the iris, ciliary body, or choroid, collectively referred to as the uvea. Tumors arise from the pigment cells (melanocytes) that reside within the uvea giving color to the eye.

Uveal melanoma (UM) can be classified by gene expression profiling (GEP) into Class 1 (low metastatic risk) and Class 2 (high metastatic risk), the latter being strongly associated with mutational inactivation of the tumor suppressor gene BRCA1 Associated Protein-1 (Ubiquitin Carboxy-Terminal Hydrolase (BAP1).

Scientists at the University of Miami Miller School of Medicine (Miami, FL, USA) performed genome-wide analysis of messenger ribonucleic acid (mRNA) isolated from five class 1 uveal melanomas that metastasized and eight class 1 tumors that did not metastasize. A total of 389 consecutive patients with UM were assigned to Class 1 or Class 2 using a prospectively validated 12-gene prognostic classifier. Selected tumors were further analyzed using global GEP and single nucleotide polymorphism microarrays. PRAME (preferentially expressed antigen in melanoma) mRNA expression was analyzed in 64 Class 1 tumors by quantitative polymerase chain reaction (PCR).

Among 64 class 1 uveal melanoma samples analyzed by quantitative PCR, 39 (61%) had low levels of PRAME mRNA (PRAME negative) and 25 (39%) had high levels of PRAME mRNA (PRAME positive). None of the patients with PRAME-negative tumors developed metastasis while seven of the patients with PRAME-positive tumors did. The 5-year actuarial rate of metastasis was 0% for Class1^PRAME−, 38% for Class1^PRAME+, and 71% for Class 2 tumors. Median metastasis-free survival for Class1^PRAME+ patients was 88 months, compared to 32 months for Class 2 patients.

J. William Harbour, MD, the senior author of the study said, “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. 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.” The study was published on March 1, 2016 in the journal Clinical Cancer Research.

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University of Miami Miller School of Medicine