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Meta-Analysis
. 2019 Oct;21(10):2167-2180.
doi: 10.1038/s41436-019-0536-8. Epub 2019 May 14.

The proportion of endometrial cancers associated with Lynch syndrome: a systematic review of the literature and meta-analysis

N A J Ryan  1   2 , M A Glaire  3 , D Blake  4 , M Cabrera-Dandy  5 , D G Evans  2   6 , E J Crosbie  7   8
Affiliations
Meta-Analysis

The proportion of endometrial cancers associated with Lynch syndrome: a systematic review of the literature and meta-analysis

N A J Ryan et al. Genet Med. 2019 Oct.

Abstract

Purpose: Endometrial cancer (EC) is often the sentinel cancer in women with Lynch syndrome (LS). However, efforts to implement universal LS screening in EC patients have been hampered by a lack of evidence detailing the proportion of EC patients that would be expected to screen positive for LS.

Methods: Studies were identified by electronic searches of Medline, Embase, Cochrane CENTRAL and Web of Science. Proportions of test positivity were calculated by random and fixed-effects meta-analysis models. I2 score was used to assess heterogeneity across studies.

Results: Fifty-three studies, including 12,633 EC patients, met the inclusion criteria. The overall proportion of endometrial tumors with microsatellite instability or mismatch repair (MMR) deficiency by immunohistochemistry (IHC) was 0.27 (95% confidence interval [CI] 0.25-0.28, I2: 71%) and 0.26 (95% CI 0.25-0.27, I2: 88%), respectively. Of those women with abnormal tumor testing, 0.29 (95% CI 0.25-0.33, I2: 83%) had LS-associated pathogenic variants on germline testing; therefore around 3% of ECs can be attributed to LS. Preselection of EC cases did increase the proportion of germline LS diagnoses.

Conclusion: The current study suggests that prevalence of LS in EC patients is approximately 3%, similar to that of colorectal cancer patients; therefore our data support the implementation of universal EC screening for LS.

Keywords: Lynch syndrome; endometrial cancer; microsatellite instability (MSI); mismatch repair (MMR) immunohistochemistry; systematic review.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Flowchart detailing study identification, study selection, and characteristics of included studies. IHC immunohistochemistry, MSI microsatellite instability.
Fig. 2
Fig. 2
Forest plot and meta-analysis of the proportion of endometrial tumors with mismatch repair deficiency by immunohistochemistry, including those that did and did not preselect tumors for testing. CI confidence interval.
Fig. 3
Fig. 3
Forest plot and meta-analysis of the proportion of endometrial tumors showing microsatellite instability, including those that did and did not preselect tumors for testing. CI confidence interval.
Fig. 4
Fig. 4
Forest plot and meta-analysis of the proportion of pathogenic variants in mismatch repairs (MMR) genes found in women with endometrial tumors showing mismatch repair deficiency and/or microsatellite instability, including studies that did and did not preselect women for testing. CI confidence interval.
See this image and copyright information in PMC

References

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