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The frequency of POLE-mutation in endometrial carcinoma and prognostic implications: a systemic review and meta-analysis

Journal of Pathology and Translational Medicine 2020년 54권 6호 p.471 ~ 479
Jumaah Alaa Salah, Salim Mais Muhammed, Al-Haddad Hawraa Sahib, McAllister Katherine Ann, Yasseen Akeel Abed,
소속 상세정보
 ( Jumaah Alaa Salah ) - University of Kufa Faculty of Medicine Department of Pathology and Forensic Medicine
 ( Salim Mais Muhammed ) - University of Kufa Faculty of Medicine Department of Pathology and Forensic Medicine
 ( Al-Haddad Hawraa Sahib ) - Al-Furat Al-Awsat Hospital
 ( McAllister Katherine Ann ) - University of Ulster School of Biomedical Sciences
 ( Yasseen Akeel Abed ) - University of Kufa Faculty of Medicine Department of Pathology and Forensic Medicine

Abstract


Background: Endometrial carcinoma (EC) is classified into four distinct molecular subgroups including ultramutated DNA polymerase epsilon (POLE). POLE-mutated tumors have the best prognosis and are a promising target for immunotherapy. This meta-analysis consolidated the reported variation of POLE-mutant frequency and assessed prognostic value in EC.

Methods: Internet searches explored scientific data bases: EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials databases. Data was extracted from eligible studies including: sample size, number of positive POLE-mutant cases, sequencing information, clinicopathologic data, and survival data. Meta-analysis and a random-effects model produced pooled estimates of POLE frequency and prognostic parameters using 95% confidence intervals (CI), hazard ratios (HR), and odd ratios (OR).

Results: Six thousand three hundred and forty-six EC patient cases were pooled from 25 studies. The pooled proportion of POLE gene mutation in EC was 8.59% (95% CI, 7.01 to 10.32), of which 8.22% (95% CI, 6.27 to 10.42) were type I and 0.93% (95% CI, 0.34 to 1.81) type 2. Clinicopathologic data showed that POLE-mutated tumors are mostly endometrioid. They present at higher levels in earlier stages (I?II) of EC (89.51%; 95% CI, 81.11 to 95.66) at the highest grade III (51.53%; 95% CI, 36.08 to 66.84) with reduced myometrial invasion (OR, 1.48, 95% CI, 0.99 to 2.20). Survival analysis indicated favorable overall survival (HR, 0.90), disease-specific survival (HR, 0.41), and progression-free survival (HR, 0.23) for POLE mutant EC.

Conclusions: Almost one-tenth of EC patients have POLE-mutated tumors. Given their improved prognostic potential, identifying the POLE mutation status is key for the management of EC patients.

키워드

Endometrial carcinoma; POLE gene

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