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

Autor: Teri A. Longacre, James M. Ford, Kerry Kingham, Rachel Hodan, Allison W. Kurian, Ann K. Folkins, Kristina Cotter
Rok vydání: 2020
Předmět:
0301 basic medicine
Cancer Research
germline
Gastroenterology
DNA Mismatch Repair
0302 clinical medicine
PMS2
Peritoneal Neoplasms
Original Research
Ovarian Neoplasms
Incidence (epidemiology)
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Prognosis
Lynch syndrome
mismatch repair
ovarian cancer
Oncology
030220 oncology & carcinogenesis
Cohort
universal tumor screening
Female
Microsatellite Instability
Adult
medicine.medical_specialty
congenital
hereditary
and neonatal diseases and abnormalities
lcsh:RC254-282
03 medical and health sciences
Germline mutation
Internal medicine
medicine
Biomarkers
Tumor
Fallopian Tube Neoplasms
Humans
Radiology
Nuclear Medicine and imaging
Germ-Line Mutation
Aged
business.industry
Clinical Cancer Research
DNA Methylation
medicine.disease
Colorectal Neoplasms
Hereditary Nonpolyposis
digestive system diseases
MSH6
030104 developmental biology
DNA Repair Enzymes
MSH2
Ovarian cancer
business
Follow-Up Studies
Zdroj: Cancer Medicine
Cancer Medicine, Vol 10, Iss 3, Pp 1012-1017 (2021)
ISSN: 2045-7634
Popis: 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.
The majority of mismatch repair deficient ovarian cancer in this cohort was due to a Lynch syndrome (LS) germline pathogenic variant. Clinicians should consider germline testing for LS for all women with epithelial ovarian cancer.
Databáze: OpenAIRE
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