Journal of Pathology and Translational Medicine

Original Articles

Mismatch repair deficiency and clinicopathological characteristics in endometrial carcinoma: a systematic review and meta-analysis: Alaa Salah Jumaah, Hawraa Sahib Al-Haddad, Mais Muhammed Salem, Katherine Ann McAllister, Akeel Abed Yasseen; J Pathol Transl Med. 2021;55(3):202-211. Published online April 14, 2021; DOI: https://doi.org/10.4132/jptm.2021.02.19

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Background
Loss of mismatch repair (MMR) occurs frequently in endometrial carcinoma (EC) and is an important prognostic marker. However, the frequency of MMR deficiency (D-MMR) in EC remains inconclusive. This systematic review and meta-analysis addressed this inconsistency and evaluated related clinicopathology.
Methods
Electronic databases were searched for articles: PubMed, Science Direct, Web of Science, EMBASE, and the Wiley Online Library. Data were extracted from 25 EC studies of D-MMR to generate a clinical dataset of 7,459 patients. A random-effects model produced pooled estimates of D-MMR EC frequency with 95% confidence interval (CI) for meta-analysis.
Results
The overall pooled proportion of D-MMR was 24.477% (95% CI, 21.022 to 28.106) in EC. The Lynch syndrome subgroup had 22.907% pooled D-MMR (95% CI, 14.852 to 32.116). D-MMR was highest in type I EC (25.810) (95% CI, 22.503 to 29.261) compared to type II (13.736) (95% CI, 8.392 to 20.144). Pooled D-MMR was highest at EC stage and grades I–II (79.430% and 65.718%, respectively) and lowest in stages III–IV and grade III (20.168% and 21.529%). The pooled odd ratios comparing D-MMR to proficient MMR favored low-stage EC disease (1.565; 0.894 to 2.740), lymphovascular invasion (1.765; 1.293 to 2.409), and myometrial invasion >50% (1.271; 0.871 to 1.853).
Conclusions
Almost one-quarter of EC patients present with D-MMR tumors. The majority has less aggressive endometrioid histology. D-MMR presents at lower tumor stages compared to MMR-proficient cases in EC. However other metastatic parameters are comparatively higher in the D-MMR disease setting.

Citations

Citations to this article as recorded by

miR-486-3p Controls the Apoptosis of Endometrial Carcinoma Cells
Donghua Wang, Xiaoli Liu, Lirong Cao, Shixiong Gong, Yi He, Xiangbin Jiang, Zhongxian Wang
Journal of Biomaterials and Tissue Engineering.2022; 12(5): 1002. CrossRef
The Role of Immunohistochemistry Markers in Endometrial Cancer with Mismatch Repair Deficiency: A Systematic Review
Amelia Favier, Justine Varinot, Catherine Uzan, Alex Duval, Isabelle Brocheriou, Geoffroy Canlorbe
Cancers.2022; 14(15): 3783. CrossRef

The frequency of POLE-mutation in endometrial carcinoma and prognostic implications: a systemic review and meta-analysis: Alaa Salah Jumaah, Mais Muhammed Salim, Hawraa Sahib Al-Haddad, Katherine Ann McAllister, Akeel Abed Yasseen; J Pathol Transl Med. 2020;54(6):471-479. Published online September 2, 2020; DOI: https://doi.org/10.4132/jptm.2020.07.23

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200 Download
9 Citations

Abstract PDF Supplementary Material

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.

Citations

Citations to this article as recorded by

Fast and reliable Sanger POLE sequencing protocol in FFPE tissues of endometrial cancer
Izabela Laczmanska, Dagmara Michalowska, Marcin Jedryka, Dorota Blomka, Mariola Semeniuk, Ewelina Czykalko, Mariola Abrahamowska, Paulina Mlynarczykowska, Agnieszka Chrusciel, Ireneusz Pawlak, Adam Maciejczyk
Pathology - Research and Practice.2023; 242: 154315. CrossRef
Uterine Neoplasms, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology
Nadeem Abu-Rustum, Catheryn Yashar, Rebecca Arend, Emma Barber, Kristin Bradley, Rebecca Brooks, Susana M. Campos, Junzo Chino, Hye Sook Chon, Christina Chu, Marta Ann Crispens, Shari Damast, Christine M. Fisher, Peter Frederick, David K. Gaffney, Robert
Journal of the National Comprehensive Cancer Network.2023; 21(2): 181. CrossRef
The clinicopathology and survival characteristics of patients with POLE proofreading mutations in endometrial carcinoma: A systematic review and meta-analysis
Alaa Salah Jumaah, Hawraa Sahib Al-Haddad, Katherine Ann McAllister, Akeel Abed Yasseen, Manish S. Patankar
PLOS ONE.2022; 17(2): e0263585. CrossRef
Enhanced polymerase activity permits efficient synthesis by cancer-associated DNA polymerase ϵ variants at low dNTP levels
Stephanie R Barbari, Annette K Beach, Joel G Markgren, Vimal Parkash, Elizabeth A Moore, Erik Johansson, Polina V Shcherbakova
Nucleic Acids Research.2022; 50(14): 8023. CrossRef
The Role of Immunohistochemistry Markers in Endometrial Cancer with Mismatch Repair Deficiency: A Systematic Review
Amelia Favier, Justine Varinot, Catherine Uzan, Alex Duval, Isabelle Brocheriou, Geoffroy Canlorbe
Cancers.2022; 14(15): 3783. CrossRef
The clinicopathological characteristics of POLE-mutated/ultramutated endometrial carcinoma and prognostic value of POLE status: a meta-analysis based on 49 articles incorporating 12,120 patients
Qing Wu, Nianhai Zhang, Xianhe Xie
BMC Cancer.2022;[Epub] CrossRef
Mismatch repair deficiency and clinicopathological characteristics in endometrial carcinoma: a systematic review and meta-analysis
Alaa Salah Jumaah, Hawraa Sahib Al-Haddad, Mais Muhammed Salem, Katherine Ann McAllister, Akeel Abed Yasseen
Journal of Pathology and Translational Medicine.2021; 55(3): 202. CrossRef
Evaluation of treatment effects in patients with endometrial cancer and POLE mutations: An individual patient data meta‐analysis
Jessica N. McAlpine, Derek S. Chiu, Remi A. Nout, David N. Church, Pascal Schmidt, Stephanie Lam, Samuel Leung, Stefania Bellone, Adele Wong, Sara Y. Brucker, Cheng Han Lee, Blaise A. Clarke, David G. Huntsman, Marcus Q. Bernardini, Joanne Ngeow, Alessand
Cancer.2021; 127(14): 2409. CrossRef
Endometrial cancer
Vicky Makker, Helen MacKay, Isabelle Ray-Coquard, Douglas A. Levine, Shannon N. Westin, Daisuke Aoki, Ana Oaknin
Nature Reviews Disease Primers.2021;[Epub] CrossRef

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