Prevalence of Lynch syndrome in women with mismatch repair-deficient ovarian cancer.
Adult
Aged
Biomarkers, Tumor
/ genetics
Colorectal Neoplasms, Hereditary Nonpolyposis
/ epidemiology
DNA Methylation
DNA Mismatch Repair
DNA Repair Enzymes
/ deficiency
Fallopian Tube Neoplasms
/ complications
Female
Follow-Up Studies
Germ-Line Mutation
Humans
Microsatellite Instability
Middle Aged
Ovarian Neoplasms
/ complications
Peritoneal Neoplasms
/ complications
Prognosis
Lynch syndrome
germline
mismatch repair
ovarian cancer
universal tumor screening
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
14
09
2020
revised:
13
11
2020
accepted:
06
12
2020
pubmed:
29
12
2020
medline:
20
7
2021
entrez:
28
12
2020
Statut:
ppublish
Résumé
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). 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 33369189
doi: 10.1002/cam4.3688
pmc: PMC7897945
doi:
Substances chimiques
Biomarkers, Tumor
0
DNA Repair Enzymes
EC 6.5.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1012-1017Informations de copyright
© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Références
Genet Test Mol Biomarkers. 2014 Apr;18(4):229-35
pubmed: 24592941
Int J Oncol. 2014 Jul;45(1):77-81
pubmed: 24788313
Gynecol Oncol. 2015 Apr;137(1):86-92
pubmed: 25622547
Genet Med. 2020 Jan;22(1):15-25
pubmed: 31337882
Gynecol Oncol. 2018 Dec;151(3):481-488
pubmed: 30322717
J Hum Genet. 2019 Aug;64(8):729-740
pubmed: 31089268
Br J Cancer. 2012 Nov 6;107(10):1783-90
pubmed: 23047549
N Engl J Med. 2006 Jun 29;354(26):2751-63
pubmed: 16807412
Anticancer Res. 2012 Nov;32(11):4963-9
pubmed: 23155266
J Clin Oncol. 2019 May 20;37(15):1305-1315
pubmed: 30964716
Am J Surg Pathol. 2016 May;40(5):656-63
pubmed: 26813747
Am J Surg Pathol. 2008 Jul;32(7):1029-37
pubmed: 18469706
J Gynecol Oncol. 2018 May;29(3):e29
pubmed: 29400022
N Engl J Med. 2003 Mar 6;348(10):919-32
pubmed: 12621137
Eur J Hum Genet. 2015 Aug;23(8):1080-4
pubmed: 25370038
Lancet Oncol. 2011 Jan;12(1):49-55
pubmed: 21145788
Gynecol Oncol. 2020 Mar;156(3):669-675
pubmed: 31924330
JAMA Oncol. 2018 Aug 1;4(8):1066-1072
pubmed: 29801090
Cancer Genet. 2016 Apr;209(4):130-7
pubmed: 26908360
J Clin Oncol. 2019 Feb 1;37(4):286-295
pubmed: 30376427