{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:37:12Z","timestamp":1786977432105,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T00:00:00Z","timestamp":1597708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000015","name":"Canadian Cancer Society Research Institute","doi-asserted-by":"publisher","award":["704038"],"award-info":[{"award-number":["704038"]}],"id":[{"id":"10.13039\/501100000015","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2020,11,15]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>For 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Women 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 215 women, germline data were available for 189 (88%); 13 women (7%) had pathogenic germline variants with 7 women with mutS homolog 6 (\n                      <jats:italic>MSH6<\/jats:italic>\n                      ); 3 women with mutL homolog 1 (\n                      <jats:italic>MLH1<\/jats:italic>\n                      ); 2 women with PMS1 homolog 2, mismatch repair system component (\n                      <jats:italic>PMS2<\/jats:italic>\n                      ); and 1 woman with mutS homolog 2 (\n                      <jats:italic>MSH2<\/jats:italic>\n                      ). A total of 28 women had MMR\u2010deficient tumors (13%); of these, 11 had pathogenic variants (39%). Sequential IHC (with\n                      <jats:italic>MLH1<\/jats:italic>\n                      promoter methylation analysis on MLH1\u2010deficient tumors) followed by MSI for nonmethylated and\/or MMR\u2010intact patients was the most sensitive (92.3%; 95% confidence interval, 64%\u201099.8%) and specific (97.7%; 95% confidence interval, 94.2%\u201099.4%) approach, missing 1 case of LS. IHC with\n                      <jats:italic>MLH1<\/jats:italic>\n                      promoter methylation analysis missed 2 patients of LS. Family history was found to have the lowest sensitivity at 55%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Sequential IHC (with\n                      <jats:italic>MLH1<\/jats:italic>\n                      promoter methylation analysis) followed by MSI was found to be most sensitive. However, IHC with\n                      <jats:italic>MLH1<\/jats:italic>\n                      promoter methylation analysis also performed well and is likely more cost\u2010effective and efficient in the clinical setting. The pretest probability of LS is high in patients with MMR deficiency and warrants universal screening for LS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.33144","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T00:59:13Z","timestamp":1598576353000},"page":"4886-4894","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Performance characteristics of screening strategies to identify Lynch syndrome in women with ovarian cancer"],"prefix":"10.1002","volume":"126","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5694-5439","authenticated-orcid":false,"given":"Soyoun Rachel","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Gynecologic Oncology Princess Margaret Cancer Centre, University Health Network Sinai Health Systems Toronto Ontario Canada"},{"name":"Department of Obstetrics and Gynaecology University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Tone","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology Princess Margaret Cancer Centre, University Health Network Sinai Health Systems Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond H.","family":"Kim","sequence":"additional","affiliation":[{"name":"Fred A. Litwin Family Centre for Genetic Medicine University Health Network Toronto Ontario Canada"},{"name":"Zane Cohen Centre for Digestive Diseases, Familial Gastrointestinal Cancer Registry Mount Sinai Hospital Toronto Ontario Canada"},{"name":"Division of Medical Oncology and Hematology Princess Margaret Cancer Centre, University Health Network Sinai Health Systems Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Cesari","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blaise A.","family":"Clarke","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto Toronto Ontario 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