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Prevalence of Lynch syndrome in women with mismatch repair‐deficient ovarian cancer

BACKGROUND: There are limited data on the prevalence of Lynch syndrome (LS) in women with primary ovarian cancer with mismatch repair deficiency (MMR‐D) by immunohistochemistry (IHC). MATERIALS AND METHODS: Three hundred and eight cases of primary ovarian, fallopian, and peritoneal cancer between Ja...

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Autores principales: Hodan, Rachel, Kingham, Kerry, Cotter, Kristina, Folkins, Ann K., Kurian, Allison W., Ford, James M., Longacre, Teri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897945/
https://www.ncbi.nlm.nih.gov/pubmed/33369189
http://dx.doi.org/10.1002/cam4.3688
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author Hodan, Rachel
Kingham, Kerry
Cotter, Kristina
Folkins, Ann K.
Kurian, Allison W.
Ford, James M.
Longacre, Teri
author_facet Hodan, Rachel
Kingham, Kerry
Cotter, Kristina
Folkins, Ann K.
Kurian, Allison W.
Ford, James M.
Longacre, Teri
author_sort Hodan, Rachel
collection PubMed
description BACKGROUND: There are limited data on the prevalence of Lynch syndrome (LS) in women with primary ovarian cancer with mismatch repair deficiency (MMR‐D) by immunohistochemistry (IHC). MATERIALS AND METHODS: Three hundred and eight cases of primary ovarian, fallopian, and peritoneal cancer between January 2012 and December 2019 were evaluated for MMR‐D by IHC. The incidence of LS in this cohort was evaluated. RESULTS: MMR‐D by IHC was identified in 16 of 308 (5.2%) (95% CI: 3.2%–8.3%) primary ovarian‐related cancers. Most cases with MMR‐D were endometrioid (n = 11, 68.7%); (95% CI: 44.2%–86.1%). MSH2/MSH6 protein loss was detected in eight cases (50.0%); (95% CI: 28.0%–72.0%) and MLH1/PMS2 protein loss was detected in four cases (25.0%); (95% CI: 9.7%–50.0%). MSH6 protein loss was detected in two cases (12.5%); (95% CI: 2.2%–37.3%) and PMS2 protein loss was detected in two cases (12.5%); (95% CI: 2.2%–37.3%). All four cases with MLH1/PMS2 protein loss had MLH1 promotor hypermethylation. All 12 women with ovarian cancer suggestive of LS underwent germline testing and 8 (66.6%); (95% CI: 38.8%–86.5%) were confirmed to have LS. CONCLUSIONS: Most ovarian cancers with somatic MMR‐D were confirmed to have LS in this cohort. Germline testing for LS in addition to BRCA1/2 for all women with an epithelial ovarian cancer would be efficient and would approach 100% sensitivity for identifying Lynch syndrome. Utilization of a multigene panel should also be considered, given the additional non‐Lynch germline mutation identified in this cohort.
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spelling pubmed-78979452021-02-23 Prevalence of Lynch syndrome in women with mismatch repair‐deficient ovarian cancer Hodan, Rachel Kingham, Kerry Cotter, Kristina Folkins, Ann K. Kurian, Allison W. Ford, James M. Longacre, Teri Cancer Med Clinical Cancer Research BACKGROUND: There are limited data on the prevalence of Lynch syndrome (LS) in women with primary ovarian cancer with mismatch repair deficiency (MMR‐D) by immunohistochemistry (IHC). MATERIALS AND METHODS: Three hundred and eight cases of primary ovarian, fallopian, and peritoneal cancer between January 2012 and December 2019 were evaluated for MMR‐D by IHC. The incidence of LS in this cohort was evaluated. RESULTS: MMR‐D by IHC was identified in 16 of 308 (5.2%) (95% CI: 3.2%–8.3%) primary ovarian‐related cancers. Most cases with MMR‐D were endometrioid (n = 11, 68.7%); (95% CI: 44.2%–86.1%). MSH2/MSH6 protein loss was detected in eight cases (50.0%); (95% CI: 28.0%–72.0%) and MLH1/PMS2 protein loss was detected in four cases (25.0%); (95% CI: 9.7%–50.0%). MSH6 protein loss was detected in two cases (12.5%); (95% CI: 2.2%–37.3%) and PMS2 protein loss was detected in two cases (12.5%); (95% CI: 2.2%–37.3%). All four cases with MLH1/PMS2 protein loss had MLH1 promotor hypermethylation. All 12 women with ovarian cancer suggestive of LS underwent germline testing and 8 (66.6%); (95% CI: 38.8%–86.5%) were confirmed to have LS. CONCLUSIONS: Most ovarian cancers with somatic MMR‐D were confirmed to have LS in this cohort. Germline testing for LS in addition to BRCA1/2 for all women with an epithelial ovarian cancer would be efficient and would approach 100% sensitivity for identifying Lynch syndrome. Utilization of a multigene panel should also be considered, given the additional non‐Lynch germline mutation identified in this cohort. John Wiley and Sons Inc. 2020-12-25 /pmc/articles/PMC7897945/ /pubmed/33369189 http://dx.doi.org/10.1002/cam4.3688 Text en © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical Cancer Research
Hodan, Rachel
Kingham, Kerry
Cotter, Kristina
Folkins, Ann K.
Kurian, Allison W.
Ford, James M.
Longacre, Teri
Prevalence of Lynch syndrome in women with mismatch repair‐deficient ovarian cancer
title Prevalence of Lynch syndrome in women with mismatch repair‐deficient ovarian cancer
title_full Prevalence of Lynch syndrome in women with mismatch repair‐deficient ovarian cancer
title_fullStr Prevalence of Lynch syndrome in women with mismatch repair‐deficient ovarian cancer
title_full_unstemmed Prevalence of Lynch syndrome in women with mismatch repair‐deficient ovarian cancer
title_short Prevalence of Lynch syndrome in women with mismatch repair‐deficient ovarian cancer
title_sort prevalence of lynch syndrome in women with mismatch repair‐deficient ovarian cancer
topic Clinical Cancer Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897945/
https://www.ncbi.nlm.nih.gov/pubmed/33369189
http://dx.doi.org/10.1002/cam4.3688
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