The prevalence of mismatch repair deficiency in ovarian cancer: A systematic review and meta-analysis
Ovarian cancer (OC) is the least survivable gynecological malignancy and presents late. Five-year survival for OC is around 45% increasing the need for innovative treatments. Checkpoint inhibitors have shown significant clinical efficacy in mismatch repair deficient (MMRd) cancers and could be a powerful treatment in OC. However, their application in OC is limited due to the lack of data on the prevalence of MMRd. The aim of our study was to conduct a systematic review of the literature and meta-analysis to provide an accurate estimate of the prevalence of MMRd in OC. We followed PRISMA guidelines throughout. Studies were identified by electronic searches of Medline, Embase, Cochrane CENTRAL and Web of Science followed by citation searching. Studies not written in English were excluded. All studies were reviewed by at least two independent reviewers. Proportions of test positivity were calculated by random and fixed-effects meta-analysis models. I2 score was used to assess heterogeneity across studies. In total 54 studies were included with 17532 analyzed for MMRd. The overall proportions of MMRd by immunohistochemistry and microsatellite instability analysis were 6.7% and 10.4%, respectively. MMRd was reported in all histotypes of epithelial OC but was most common in endometrioid OC. We estimate that on average 46.7% (95% CI: 28.8-65.4) of ovarian carcinomas showing MMRd by IHC had a germline path_MMR variant identified. OC in those with Lynch syndrome seems to present at an earlier age and stage. Studies however were generally of low quality and there was a high degree of heterogeneity. A significant minority (up to 16%) of OC displays MMRd and, therefore, could be amenable to checkpoint inhibition therapy. However, the current literature base is of limited quality and therefore high-quality prospective studies exploring MMRd in OC with the use of multimodal testing are required. In addition, trials researching efficacy of checkpoint inhibition in MMRd OC are needed.
Citation
@article{a.2022,
author = {Atwal, A. and Snowsill, T. and Dandy, M. C. and Krum, T. and
Newton, C. and Evans, D. G. and Crosbie, E. J. and Ryan, N. A. J.},
title = {The Prevalence of Mismatch Repair Deficiency in Ovarian
Cancer: {A} Systematic Review and Meta-Analysis},
journal = {International Journal of Cancer},
volume = {151},
number = {9},
pages = {1626-1639},
date = {2022},
url = {https://tristansnowsill.co.uk/the-prevalence-of-mismatch-repair-deficiency.html},
doi = {https://doi.org/10.1002/ijc.34165},
langid = {en},
abstract = {Ovarian cancer (OC) is the least survivable gynecological
malignancy and presents late. Five-year survival for OC is around
45\% increasing the need for innovative treatments. Checkpoint
inhibitors have shown significant clinical efficacy in mismatch
repair deficient (MMRd) cancers and could be a powerful treatment in
OC. However, their application in OC is limited due to the lack of
data on the prevalence of MMRd. The aim of our study was to conduct
a systematic review of the literature and meta-analysis to provide
an accurate estimate of the prevalence of MMRd in OC. We followed
PRISMA guidelines throughout. Studies were identified by electronic
searches of Medline, Embase, Cochrane CENTRAL and Web of Science
followed by citation searching. Studies not written in English were
excluded. All studies were reviewed by at least two independent
reviewers. Proportions of test positivity were calculated by random
and fixed-effects meta-analysis models. I2 score was used to assess
heterogeneity across studies. In total 54 studies were included with
17532 analyzed for MMRd. The overall proportions of MMRd by
immunohistochemistry and microsatellite instability analysis were
6.7\% and 10.4\%, respectively. MMRd was reported in all histotypes
of epithelial OC but was most common in endometrioid OC. We estimate
that on average 46.7\% (95\% CI: 28.8-65.4) of ovarian carcinomas
showing MMRd by IHC had a germline path\_MMR variant identified. OC
in those with Lynch syndrome seems to present at an earlier age and
stage. Studies however were generally of low quality and there was a
high degree of heterogeneity. A significant minority (up to 16\%) of
OC displays MMRd and, therefore, could be amenable to checkpoint
inhibition therapy. However, the current literature base is of
limited quality and therefore high-quality prospective studies
exploring MMRd in OC with the use of multimodal testing are
required. In addition, trials researching efficacy of checkpoint
inhibition in MMRd OC are needed.}
}