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Testing for lynch syndrome in people with endometrial cancer using immunohistochemistry and microsatellite instability-based testing strategies – a systematic review of test accuracy

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Stinton, Chris, Fraser, Hannah, Al-Khudairy, Lena, Court, Rachel A., Jordan, Mary, Grammatopoulos, Dimitris and Taylor-Phillips, Sian (2020) Testing for lynch syndrome in people with endometrial cancer using immunohistochemistry and microsatellite instability-based testing strategies – a systematic review of test accuracy. Gynecologic Oncology . doi:10.1016/j.ygyno.2020.10.003 (In Press)

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Official URL: https://doi.org/10.1016/j.ygyno.2020.10.003

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Abstract

Background
Lynch syndrome is an inherited genetic condition that is associated with an increased risk of cancer, including endometrial and colorectal cancer. We assessed the test accuracy of immunohistochemistry and microsatellite instability-based testing (with or without MLH1 promoter methylation testing) for Lynch syndrome in women with endometrial cancer.

Methods
We conducted a systematic review of literature published up to August 2019. We searched bibliographic databases, contacted experts and checked reference lists of relevant studies. Two reviewers conducted each stage of the review.

Results
Thirteen studies were identified that included approximately 3500 participants. None of the studies was at low risk of bias in all domains. Data could not be pooled due to the small number of heterogeneous studies. Sensitivity ranged from 60.7–100% for immunohistochemistry, 41.7–100% for microsatellite instability-based testing, and 90.5–100% for studies combining immunohistochemistry, microsatellite instability-based testing, and MLH1 promoter methylation testing. Specificity ranged from 60.9–83.3% (excluding 1 study with highly selective inclusion criteria) for immunohistochemistry, 69.2–89.9% for microsatellite instability-based testing, and 72.4–92.3% (excluding 1 study with highly selective inclusion criteria) for testing strategies that included immunohistochemistry, microsatellite instability-based testing, and MLH1 promoter methylation. We found no statistically significant differences in test accuracy estimates (sensitivity, specificity) in head-to-head studies of immunohistochemistry versus microsatellite instability-based testing. Reported test failures were rare.

Conclusions
Sensitivity of the index tests were generally high, though most studies had much lower specificity. We found no evidence that test accuracy differed between IHC and MSI based strategies. The evidence base is currently small and at high risk of bias.

Item Type: Journal Article
Subjects: Q Science > QH Natural history
R Medicine > RB Pathology
R Medicine > RC Internal medicine
Divisions: Faculty of Medicine > Warwick Medical School
SWORD Depositor: Library Publications Router
Library of Congress Subject Headings (LCSH): Colon (Anatomy) -- Cancer -- Genetic aspects, Rectum -- Cancer -- Genetic aspects, Endometrium -- Cancer -- Diagnosis, Immunohistochemistry , Microsatellites (Genetics)
Journal or Publication Title: Gynecologic Oncology
Publisher: Academic Press
ISSN: 0090-8258
Official Date: 24 October 2020
Dates:
DateEvent
24 October 2020Available
5 October 2020Accepted
Date of first compliant deposit: 13 November 2020
DOI: 10.1016/j.ygyno.2020.10.003
Status: Peer Reviewed
Publication Status: In Press
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
129546[NIHR] National Institute for Health Researchhttp://dx.doi.org/10.13039/501100000272
CDF-2016-09-018[NIHR] National Institute for Health Researchhttp://dx.doi.org/10.13039/501100000272

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