Comparison of PRAME antigen detection by Immunohistochemistry (IHC) and polymerase chain reaction (PCR) in Uveal Melanoma.

Abstract

Purpose : Uveal melanomas (UM) are the most common primary intraocular malignancy in the adult population. Based on gene expression profiles, UM can be categorized as Class 1 (low risk for metastasis) or Class 2 (high risk for metastasis). PRAME (PReferentially expressed Antigen in MElanoma) protein is a member of the cancer-testis antigen family and has been suggested as an independent UM prognostic biomarker. PRAME can be detected in UM tissue by either RT-PCR or IHC but concordance in techniques has not been determined.

Methods : We retrospectively identified UM patients who had PRAME detected on RT-PCR testing (Decision Dx UM PRAME, Castle Biosciences, TX) following globe enucleation. In house PRAME IHC was performed on these specimens with cutoff of 50% for positive detection after slide review. ICH results, based on clinical stage, were compared.

Results : 15 UM patients (11 males (73%), average age 60.7 years) were analyzed. AJCC 8th edition staging was varied (Stage 1 n=2), Stage 2 (n=6), Stage 3 (n=6), Stage 4 (n=1) and Class 1 in 9 eyes (60%) and Class 2 in 6 eyes (40%). 11/15 (73%) cases showed concordant PRAME detection results by both RT-PCR and IHC. In 4/15 (27%) discordant cases, ICH did not reach significance for PRAME positivity. Tumor grade for these cases included 1a, 2b, 3d and 4e and 3 cases were low risk Class 1. No patients with discordance developed metastatic disease with 13 months mean last follow up (range 0.1-17 months).

Conclusions : Our findings reveal that PRAME RT-PCR and IHC provide concordant results in 73% of enucleated UM eyes. The discordant results differed in tumor stage and may be due to a lack uniform standardization of IHC based nuclear PRAME detection or geospatial variations within each tumor. Further studies are required to determine the methodologic and prognostic implications.

This is a 2021 ARVO Annual Meeting abstract.