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. 2017 Dec 8;17(1):836.
doi: 10.1186/s12885-017-3820-5.

A systematic review of test accuracy studies evaluating molecular micro-satellite instability testing for the detection of individuals with lynch syndrome

Helen Coelho  1 , Tracey Jones-Hughes  2 , Tristan Snowsill  2 , Simon Briscoe  2 , Nicola Huxley  2 , Ian M Frayling  3 , Chris Hyde  2
Affiliations

A systematic review of test accuracy studies evaluating molecular micro-satellite instability testing for the detection of individuals with lynch syndrome

Helen Coelho et al. BMC Cancer. .

Abstract

Background: A systematic review was conducted to assess the diagnostic test accuracy of polymerase chain reaction (PCR)-based microsatellite instability (MSI) testing for identifying Lynch syndrome in patients with colorectal cancer (CRC). Unlike previous reviews, this was based on assessing MSI testing against best practice for the reference standard, and included CRC populations that were unselected, age-limited or high-risk for Lynch syndrome.

Methods: Single- and two-gate diagnostic test accuracy studies, or similar, were identified, assessed for inclusion, data extracted and quality appraised by two reviewers according to a pre-specified protocol. Sensitivity of MSI testing was estimated for all included studies. Specificity, likelihood ratios and predictive values were estimated for studies that were not based on high-risk samples. Narrative synthesis was conducted.

Results: Nine study samples were included. When MSI-Low results were considered to be negative, sensitivity estimates ranged from 67% (95% CI 47, 83) to 100% (95% CI 94, 100). Three studies contributed to estimates of both sensitivity and specificity, with specificity ranging from 61% (95% CI 57, 65), to 93% (95% CI 89, 95). Good sensitivity was achieved at the expense of specificity. When MSI-L was considered to be positive (effectively lowering the threshold for a positive index test result) sensitivity increased and specificity decreased. Between-study heterogeneity in both the MSI and reference standard testing, combined with the low number of studies contributing to both sensitivity and specificity estimates, precluded pooling by meta-analysis.

Conclusions: MSI testing is an effective screening test for Lynch syndrome. However, there is significant uncertainty surrounding what balance of sensitivity and specificity will be achieved in clinical practice and how this relates to specific characteristics of the test (such as the panel of markers used or the thresholds used to denote a positive test).

Keywords: Diagnostic testing; HNPCC; Lynch syndrome; Microsatellite instability; Systematic review; Test accuracy.

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Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Flow-chart detailing selection of studies. 1Abstracts were excluded when they not linked to an included study and did not provide sufficient methodological information to meet the review inclusion criteria or have data extracted. 2These studies evaluated IHS and not MSI. 3One of these studies included two distinct populations, both of which are included in this review. Although there are eight included studies, there are, therefore, nine included datasets
Fig. 2
Fig. 2
Summary receiver operating characteristic plots for MSI testing
See this image and copyright information in PMC

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