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KMID : 1137020220330020015
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Journal of Gynecologic Oncology
2022 Volume.33 No. 2 p.15 ~ p.15
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Clinical evaluation of a droplet digital PCR assay for detecting POLE mutations and molecular classification of endometrial cancer
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Kim Gil-Hyang
Lee Song-Kook
Suh Dong-Hoon
Kim Ki-Dong
No Jae-Hong
Kim Yong-Beom
Kim Hyo-Jin
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Abstract
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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 POLE mutations 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 sequencing/next-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.
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KEYWORD
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Polymerase Chain Reaction, POLE, Classification, Endometrial Cancer, Prognosis
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