{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T12:15:08Z","timestamp":1789820108716,"version":"4.0.1"},"reference-count":35,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"34","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> Tumor testing for microsatellite instability and\/or mismatch repair-deficiency (MSI\/IHC) and clinical prediction models effectively screen for Lynch syndrome (LS)\u2013associated colorectal cancer (CRC) and endometrial cancer (EC), but they have not been assessed for their ability to identify non-LS forms of inherited risk. The aim of this study was to compare MSI\/IHC and the PREMM<jats:sub>5<\/jats:sub> prediction model to identify carriers of LS and non-LS pathogenic variants (PVs) among patients with CRC and EC. <\/jats:p><\/jats:sec><jats:sec><jats:title>PATIENTS AND METHODS<\/jats:title><jats:p> Data were retrospectively analyzed from two single-institution cohorts: 706 patients with CRC and\/or EC referred for genetic evaluation\/testing (high-risk cohort) and 1,058 consecutively ascertained patients with CRC (oncology clinic cohort), unselected for familial risk. All participants underwent germline multigene panel testing. PREMM<jats:sub>5<\/jats:sub> scores were calculated from personal\/family cancer history. The primary outcome was the proportion of individuals with germline PVs (LS PVs, high-penetrance PVs, and any PVs) who had abnormal MSI\/IHC testing and\/or PREMM<jats:sub>5<\/jats:sub> score \u2265 2.5%. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> MSI\/IHC and PREMM<jats:sub>5<\/jats:sub> had comparable sensitivity for identifying LS carriers in high-risk (89.3% v 85.7%; P = .712) and oncology clinic patients (96.6% v 96.6%; P = 1.000), although MSI\/IHC had significantly superior specificity for LS (81.3% v 20.1%; P &lt; .001; 92.3% v 24.3%; P &lt; .001). In both cohorts, PREMM<jats:sub>5<\/jats:sub> had superior sensitivity to MSI\/IHC at identifying patients with any high-penetrance PVs and any low-, moderate-, and high-penetrance PVs. Among patients with normal MSI\/IHC, PREMM<jats:sub>5<\/jats:sub> identified 84.2% and 83.3% of high-risk patients with CRC\/EC and oncology clinic CRC patients with high-penetrance PVs, respectively. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> MSI\/IHC and PREMM<jats:sub>5<\/jats:sub> effectively identify patients with CRC and\/or EC with LS, although MSI\/IHC has better specificity for LS. Because PREMM<jats:sub>5<\/jats:sub> identifies non-LS, high-penetrance germline PVs, patients with CRC and\/or EC with PREMM<jats:sub>5<\/jats:sub> score \u2265 2.5%, including those with normal MSI\/IHC, should be offered multigene panel testing. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.20.01470","type":"journal-article","created":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T19:59:48Z","timestamp":1601495988000},"page":"4086-4094","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":12,"title":["Comparison of Colorectal and Endometrial Microsatellite Instability Tumor Analysis and Premm<sub>5<\/sub> Risk Assessment for Predicting Pathogenic Germline Variants on Multigene Panel Testing"],"prefix":"10.1200","volume":"38","author":[{"given":"Alessandro","family":"Mannucci","sequence":"first","affiliation":[{"name":"IRCCS Ospedale San Raffaele Scientific Institute, Milan, Italy"},{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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