Cargando…

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 pow...

Descripción completa

Detalles Bibliográficos
Autores principales: Atwal, Amit, Snowsill, Tristan, Dandy, Marcus Cabrera, Krum, Thomas, Newton, Claire, Evans, Dafydd Gareth, Crosbie, Emma J., Ryan, Neil A. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9539584/
https://www.ncbi.nlm.nih.gov/pubmed/35792468
http://dx.doi.org/10.1002/ijc.34165
_version_ 1784803520719880192
author Atwal, Amit
Snowsill, Tristan
Dandy, Marcus Cabrera
Krum, Thomas
Newton, Claire
Evans, Dafydd Gareth
Crosbie, Emma J.
Ryan, Neil A. J.
author_facet Atwal, Amit
Snowsill, Tristan
Dandy, Marcus Cabrera
Krum, Thomas
Newton, Claire
Evans, Dafydd Gareth
Crosbie, Emma J.
Ryan, Neil A. J.
author_sort Atwal, Amit
collection PubMed
description 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. I (2) score was used to assess heterogeneity across studies. In total 54 studies were included with 17 532 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.
format Online
Article
Text
id pubmed-9539584
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher John Wiley & Sons, Inc.
record_format MEDLINE/PubMed
spelling pubmed-95395842022-10-14 The prevalence of mismatch repair deficiency in ovarian cancer: A systematic review and meta‐analysis Atwal, Amit Snowsill, Tristan Dandy, Marcus Cabrera Krum, Thomas Newton, Claire Evans, Dafydd Gareth Crosbie, Emma J. Ryan, Neil A. J. Int J Cancer Tumor Markers and Signatures 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. I (2) score was used to assess heterogeneity across studies. In total 54 studies were included with 17 532 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. John Wiley & Sons, Inc. 2022-07-06 2022-11-01 /pmc/articles/PMC9539584/ /pubmed/35792468 http://dx.doi.org/10.1002/ijc.34165 Text en © 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Tumor Markers and Signatures
Atwal, Amit
Snowsill, Tristan
Dandy, Marcus Cabrera
Krum, Thomas
Newton, Claire
Evans, Dafydd Gareth
Crosbie, Emma J.
Ryan, Neil A. J.
The prevalence of mismatch repair deficiency in ovarian cancer: A systematic review and meta‐analysis
title The prevalence of mismatch repair deficiency in ovarian cancer: A systematic review and meta‐analysis
title_full The prevalence of mismatch repair deficiency in ovarian cancer: A systematic review and meta‐analysis
title_fullStr The prevalence of mismatch repair deficiency in ovarian cancer: A systematic review and meta‐analysis
title_full_unstemmed The prevalence of mismatch repair deficiency in ovarian cancer: A systematic review and meta‐analysis
title_short The prevalence of mismatch repair deficiency in ovarian cancer: A systematic review and meta‐analysis
title_sort prevalence of mismatch repair deficiency in ovarian cancer: a systematic review and meta‐analysis
topic Tumor Markers and Signatures
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9539584/
https://www.ncbi.nlm.nih.gov/pubmed/35792468
http://dx.doi.org/10.1002/ijc.34165
work_keys_str_mv AT atwalamit theprevalenceofmismatchrepairdeficiencyinovariancancerasystematicreviewandmetaanalysis
AT snowsilltristan theprevalenceofmismatchrepairdeficiencyinovariancancerasystematicreviewandmetaanalysis
AT dandymarcuscabrera theprevalenceofmismatchrepairdeficiencyinovariancancerasystematicreviewandmetaanalysis
AT krumthomas theprevalenceofmismatchrepairdeficiencyinovariancancerasystematicreviewandmetaanalysis
AT newtonclaire theprevalenceofmismatchrepairdeficiencyinovariancancerasystematicreviewandmetaanalysis
AT evansdafyddgareth theprevalenceofmismatchrepairdeficiencyinovariancancerasystematicreviewandmetaanalysis
AT crosbieemmaj theprevalenceofmismatchrepairdeficiencyinovariancancerasystematicreviewandmetaanalysis
AT ryanneilaj theprevalenceofmismatchrepairdeficiencyinovariancancerasystematicreviewandmetaanalysis
AT atwalamit prevalenceofmismatchrepairdeficiencyinovariancancerasystematicreviewandmetaanalysis
AT snowsilltristan prevalenceofmismatchrepairdeficiencyinovariancancerasystematicreviewandmetaanalysis
AT dandymarcuscabrera prevalenceofmismatchrepairdeficiencyinovariancancerasystematicreviewandmetaanalysis
AT krumthomas prevalenceofmismatchrepairdeficiencyinovariancancerasystematicreviewandmetaanalysis
AT newtonclaire prevalenceofmismatchrepairdeficiencyinovariancancerasystematicreviewandmetaanalysis
AT evansdafyddgareth prevalenceofmismatchrepairdeficiencyinovariancancerasystematicreviewandmetaanalysis
AT crosbieemmaj prevalenceofmismatchrepairdeficiencyinovariancancerasystematicreviewandmetaanalysis
AT ryanneilaj prevalenceofmismatchrepairdeficiencyinovariancancerasystematicreviewandmetaanalysis