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- 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
- 6,068 View
- 209 Download
- 9 Web of Science
- 8 Crossref
-
Abstract
PDF
Supplementary Material - 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
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Reitan Ribeiro, Filomena Marino Carvalho, Glauco Baiocchi, Rodrigo Santa Cruz Guindalini, Juliano Rodrigues da Cunha, Carlos Henrique dos Anjos, Caroline de Nadai Costa, Ana Carolina Leite Vieira Costa Gifoni, Renato Cagnacci Neto, Allyne Queiroz Carneiro
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А. E. Protasova, G. A. Raskin, M. S. Sobivchak
Tumors of female reproductive system.2024; 20(2): 105. CrossRef - Prevalence of Mismatch Repair Gene Defects by Means of Immuno-histochemistry Staining for MMR Proteins in Endometrial Cancer
Kaustubh Girish Burde, Indu R. Nair, Pavithran Keechilattu, Anupama Rajanbabu
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Cancers.2022; 14(15): 3783. CrossRef
- Guidelines of the Brazilian Society of Surgical Oncology for anatomopathological, immunohistochemical, and molecular testing in female tumors
- 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
- 7,112 View
- 300 Download
- 28 Web of Science
- 29 Crossref
-
Abstract
PDFSupplementary 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
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