Repeat Gene Expression Profiling, PRAME Status, and Next-Generation Sequencing Testing in Uveal Melanoma Undergoing Secondary Therapy.

Abstract

To compare first and repeat gene expression profiling (GEP) class, preferentially expressed antigen in melanoma (PRAME) status, and Next-Generation Sequencing (NGS) results in choroidal melanoma patients who required either enucleation or secondary plaque brachytherapy following initial plaque radiotherapy. Retrospective case series. In this study, 49 patients were included. 41 underwent enucleation and 8 underwent secondary plaque brachytherapy after initial plaque radiotherapy. FNAB was performed at each procedure to determine GEP class and PRAME status, as well as to obtain the NGS results, using DiagnosticDx-UM, DiagnosticDx-PRAME, and DiagnosticDx-UMSeq, respectively (Castle Biosciences, Friendswood, TX). GEP classification remained concordant between initial and secondary procedures in 41 of 49 patients (83.6%; p = 0.07). Among 31 patients with paired PRAME test results, 27 (87.1%) demonstrated concordance (p = 0.625). Notably, no changes in GEP class or PRAME status were observed among the 15 eyes enucleated for neovascular glaucoma. NGS findings remained unchanged in all 17 patients with results available from both the initial and secondary surgeries. Mean tumor thickness following the initial plaque radiotherapy was significantly greater in patients who exhibited a change in GEP class compared with those who did not (p = 0.027). Additionally, GEP discriminant scores decreased significantly after initial plaque radiotherapy (p < 0.05). The GEP class and PRAME status remain reliable markers for choroidal melanoma following plaque radiotherapy in 84% and 87% of patients, respectively. However, changes in these biomarkers may be observed in cases of tumor recurrence or resistance to plaque therapy, suggesting alterations in the tumor microenvironment as related to tumor progression.