Molecular stratification of endometrial carcinoma provides more accurate prognostic information than traditional clinicopathologic features. However, because next-generation sequencing is typically recommended for polymerase epsilon (POLE) mutation detection, the practical application of a test based on molecular stratification is limited in the clinical setting.
To evaluate a polymerase chain reaction (PCR)–based assay for POLE mutation detection in endometrial carcinoma.
We developed a PCR-based technology called Dalton Mutation Identifier Technology (Dalton-MIT) that targets 9 mutation sites within POLE exons. Endometrial carcinoma specimens from 613 patients were tested for POLE mutations. Correlations between POLE mutations with patient clinicopathologic characteristics and prognosis were analyzed.
PCR detection data showed that the incidence rate of POLE mutation was 11.4% (70 of 613). Patients with POLE mutations presented better clinicopathologic characteristics and prognosis than those with non–POLE mutations. Comparison between Dalton-MIT and next-generation sequencing in 59.5% (365 of 613) of specimens showed that the sensitivity of Dalton-MIT for detecting POLE pathogenic mutations was 100%, the specificity was 99.3%, the Youden index was .993, and the κ value was .981 (P < .001).
Our data demonstrate that POLE mutation detection by Dalton-MIT correlates with next-generation sequencing. This suggests that Dalton-MIT represents a promising alternative assay for detecting POLE mutations and will facilitate the wider application of molecular stratification tools for endometrial carcinoma in the clinic.
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Chen and Y. Li contributed equally to this work.
This study was financially supported by the National Natural Science Foundation of China (No. 82072858 to Y. Li).
The authors have no relevant financial interest in the products or companies described in this article.