A systematic review of test accuracy studies evaluating molecular micro-satellite instability testing for the detection of individuals with lynch syndrome
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).
Citation
@article{h.2017,
author = {Coelho, H. and Jones-Hughes, T. and Snowsill, T. and
Briscoe, S. and Huxley, N. and Frayling, I. M. and Hyde, C.},
title = {A Systematic Review of Test Accuracy Studies Evaluating
Molecular Micro-Satellite Instability Testing for the Detection of
Individuals with Lynch Syndrome},
journal = {BMC Cancer},
volume = {17},
number = {836},
date = {2017-12-01},
url = {https://tristansnowsill.co.uk/a-systematic-review-of-test-accuracy-studies-evaluating.html},
doi = {10.1186/s12885-017-3820-5},
langid = {en},
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).}
}