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

• Jumaah AS
• Al-Haddad HS
• Salem MM
• McAllister KA
• Yasseen AA

• KMID: 2515925
• DOI: http://doi.org/10.4132/jptm.2021.02.19

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

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

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  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.

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  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.

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