Idylla™ POLE-POLD1 mutation assay for molecular characterization and risk stratification of endometrial cancers: a...

Endometrial carcinoma (EC) is a common gynecological cancer with rising incidence driven by obesity and aging populations. Accurate and timely molecular classification is critical for guiding personalized oncology treatment, especially in early-stage high-grade endometrioid carcinoma. Here we present a large scale, retrospective multicenter validation of a novel POLE-POLD1 mutation assay for use in molecular characterization of EC. We evaluated the analytical performance and robustness of the novel Idylla™ POLE-POLD1 Mutation Assay, a cartridge-based PCR platform optimized for FFPE tissue. Performance comparators were established NGS reference methods. Overall, 544 formalin-fixed, paraffin embedded (FFPE) EC cases from diagnostic pathology of ten centers in Europe and North America were included. Of 544 samples, 520 revealed POLE-POLD1 test and comparator results, yielding an overall concordance of 97% (PPA of 0.96 and NPA of 0.98). Discordance was limited to a small number of variants and was often associated with low input material or the detection of multiple concurrent variants. The assay demonstrated robust performance across variable FFPE slice thickness (4-10 μm), number of Sects. (1-6), and tumor cell percentage (from 10% to 100%), with an assay invalid rate of only 2.76%. Moreover, the Idylla™ platform offers rapid results (~ 2 h) with minimal workflow complexity. The Idylla™ POLE-POLD1 Mutation Assay is a reliable and rapid diagnostic assay for clinically relevant molecular classification of EC, demonstrating high concordance with NGS and robust performance under routine pathology conditions. Whereas NGS provides comprehensive genomic profiling, including rare variants of unknown pathogenic significance, the Idylla™ assay targets treatment relevant pathogenic variants with rapid turnaround time, supporting timely, individualized treatment decisions.