ArticleCancer2020
Performance characteristics of screening strategies to identify Lynch syndrome in women with ovarian cancer.
Article in Cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- The prevalence of mismatch repair deficiency in ovarian cancer: A systematic review and meta-analysis.International journal of cancer · 2022Pooled it
- Molecular Classification of Endometrial Cancers Using an Integrative DNA Sequencing Panel.Journal of surgical oncology · 2025Article
- MSH2, MSH6, MLH1, and PMS2 immunohistochemistry as highly sensitive screening method for DNA mismatch repair deficiency syndromes in pediatric high-grade glioma.Acta neuropathologica · 2025Article
- Molecular Pathology of Ovarian Endometrioid Carcinoma: A Review.Oncology research · 2025Review
- Lynch syndrome screening in patients with young-onset extra-colorectal Lynch syndrome-associated cancers.International journal of clinical oncology · 2024Article
- Rare single-nucleotide variants of MLH1 and MSH2 genes in patients with Lynch syndrome.Cancer reports (Hoboken, N.J.) · 2024Article
- Article
- Performance characteristics of screening strategies to identify Lynch syndrome in women with ovarian cancer.Cancer · 2020Article
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Authors and funding
22 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundFor women with ovarian cancer (OC), the optimal screening strategy to identify Lynch syndrome (LS) has not been determined. In the current study, the authors compared the performance characteristics of various strategies combining mismatch repair (MMR) immunohistochemistry (IHC), microsatellite instability testing (MSI), and family history for the detection of LS.
methodsWomen with nonserous and/or nonmucinous ovarian cancer were recruited prospectively from 3 cancer centers in Ontario, Canada. All underwent germline testing for LS and completed a family history assessment. Tumors were assessed using MMR IHC and MSI. The sensitivity, specificity, and positive and negative predictive values of screening strategies were compared with the gold standard of a germline result.
resultsOf 215 women, germline data were available for 189 (88%); 13 women (7%) had pathogenic germline variants with 7 women with mutS homolog 6 (MSH6); 3 women with mutL homolog 1 (MLH1); 2 women with PMS1 homolog 2, mismatch repair system component (PMS2); and 1 woman with mutS homolog 2 (MSH2). A total of 28 women had MMR-deficient tumors (13%); of these, 11 had pathogenic variants (39%). Sequential IHC (with MLH1 promoter methylation analysis on MLH1-deficient tumors) followed by MSI for nonmethylated and/or MMR-intact patients was the most sensitive (92.3%; 95% confidence interval, 64%-99.8%) and specific (97.7%; 95% confidence interval, 94.2%-99.4%) approach, missing 1 case of LS. IHC with MLH1 promoter methylation analysis missed 2 patients of LS. Family history was found to have the lowest sensitivity at 55%.
conclusionsSequential IHC (with MLH1 promoter methylation analysis) followed by MSI was found to be most sensitive. However, IHC with MLH1 promoter methylation analysis also performed well and is likely more cost-effective and efficient in the clinical setting. The pretest probability of LS is high in patients with MMR deficiency and warrants universal screening for LS.
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