J Pathol Transl Med.  2021 May;55(3):202-211. 10.4132/jptm.2021.02.19.

Mismatch repair deficiency and clinicopathological characteristics in endometrial carcinoma: a systematic review and meta-analysis

Affiliations
  • 1Department of Pathology and Forensic Medicine, Faculty of Medicine, University of Kufa, Kufa, Iraq
  • 2Al-Furat Al-Awsat Hospital, Kufa, Iraq
  • 3School of Biomedical Sciences, Ulster University, Northern Ireland, UK

Abstract

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.

Keyword

Microsatellite instability; MMR-D; Endometrial carcinoma

Figure

  • Fig. 1. PRISMA flow chart for search strategy, leading to selection of 25 studies for meta-analysis.

  • Fig. 2. The D-MMR gene proportions in each study are shown by forest plot [6-30]. D-MMR, mismatch repair deficiency; CI, confidence interval; EC, endometrial carcinoma.

  • Fig. 3. D-MMR EC: type I EC (A) and type II EC (B) [8,9,11-15,17-22,24,26,29,30]. D-MMR, mismatch repair deficiency; CI, confidence interval; EC, endometrial carcinoma.


Reference

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