Clinical evaluation of a droplet digital PCR assay for detecting POLE mutations and molecular classification of endometrial cancer
- Author:
Gilhyang KIM
1
;
Song Kook LEE
;
Dong Hoon SUH
;
Kidong KIM
;
Jae Hong NO
;
Yong Beom KIM
;
Hyojin KIM
Author Information
- Publication Type:Original Article
- From:Journal of Gynecologic Oncology 2022;33(2):e15-
- CountryRepublic of Korea
- Language:English
-
Abstract:
Objective:We evaluated droplet digital polymerase chain reaction (ddPCR) method for detecting POLE mutations in endometrial cancer (EC) and guiding its molecular classification.
Methods:We reviewed 240 EC specimens from our hospital database. A ddPCR assay was used to identify POLE mutations at 5 known hotspots (P286R, S297F, V411L, A456P, and S459F). Expressions of p53 and mismatch repair proteins were identified using immunohistochemistry.
Results:The ddPCR assay identified POLEmutations in 10.8% of patients. The most common mutation was V411L (61.54%), followed by P286R (23.07%), S459F (7.69%), S297F (3.85%), and A456P (3.85%). Eight/one cases had positive ddPCR but negative Sanger sequencingext-generation sequencing, respectively. Molecular classification revealed p53-mutated subtype as significantly more common for tumors with a high International Federation of Gynecology and Obstetrics (FIGO) grade, deep myometrial invasion, lymphovascular space invasion, advanced stage, and high/advanced risk groups; the POLE mutated group was more frequent in the low stage and low/intermediate risk group. Survival analyses revealed the poorest outcomes for p53-mutated EC, while mismatch repair-deficient and no specific molecular profile ECs had similar progression-free survival (PFS) outcomes, and POLE -mutated ECs had the best PFS outcome (p<0.001). When only intermediate, high-intermediate, and high-risk groups were analyzed for subgroups, molecular classification still showed differences both in PFS (p=0.003) and overall survival (p=0.017).
Conclusion:Hotspot POLE mutations can be detected using the ddPCR assay. We suggest simultaneously evaluating POLE mutation status using ddPCR and p53/mismatch repair protein expressions using immunohistochemistry, which can rapidly and accurately determine the molecular subtype of EC.
