Prognostication for Uveal Melanoma: Are Two Tests Better than One?

Is the risk of metastasis equivalent between a class 2 tumor (GEP) and monosomy 3 tumor as determined by MLPA? The concordance between these tests in patients with uveal melanoma undergoing a prognostic fine-needle aspiration biopsy (FNAB) has not been studied until recently. In a retrospective study, GEP and FISH (44 patients) or GEP and MLPA (49 patients – 6 technical failures GEP [3] and MLPA [3] ) prognostication was performed on consecutive patients with posterior uveal melanoma (iris melanoma excluded) over a period of 2 years (2012–2014) [8] . In 43 patients, with available results of both GEP and MLPA, the GEP classification was discordant with monosomy 3 in 16% (7/43 tumors). More specifically, 19% (6/31) of the tumors categorized as class 1 (GEP) had monosomy 3, and disomy 3 was observed in 8% (1/12) of the tumors categorized as class 2. In simple terms, in 6 (19%) patients, a contradictory prognosis would have been rendered; good prognosis by GEP and bad prognosis by MLPA. Similarly, but to a lesser extent, in 1 (8%) patient, a contradictory prognosis would have been rendered; bad prognosis by GEP and good prognosis by MLPA. Several explanations have been put forward to elucidate the observed external discordance between 2 validated commercial prognostication tests. The first is the evidence of tumor heterogeneity and of internal discorOver the last 2 decades, several prognostic tests have been developed for assisting clinicians to predict the metastatic potential of uveal melanoma, including fluorescence in situ hybridization (FISH), comparative genomic hybridization, microsatellite analysis, single-nucleotide polymorphism array (SNP), multiplex ligation-dependent probe amplification (MLPA), and gene expression profiling (GEP) [1] . Naturally, the questions regarding concordance between the tests and superiority of one test over the other become relevant. There are only a few reports wherein 2 prognostic tests have been performed on a given tumor sample and results evaluated for concordance (SNP/FISH [2] , MLPA/FISH [3] , and GEP/SNP) [4] . At present, only 2 prognostication tests – MLPA (Impact Genetics, Toronto, Canada) and GEP (DecisionDxUM; Castle Biosciences, Inc., Pheonix, Arizona, USA) – are commercially available. Therefore, any comparison of these 2 tests has important implications for clinical usage. In the MLPA test, chromosome 3 loss (monosomy 3) and chromosome 8q gain are cytogenetic markers predictive of poor prognosis, and the presence of chromosome 6p gain is suggestive of good prognosis [5, 6] . On the other hand, GEP testing categorizes uveal melanoma as class 1 or class 2, corresponding to a low and a high metastatic risk, respectively [4, 7] . Received: March 14, 2017 Accepted after revision: March 15, 2017 Published online: April 14, 2017