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• W2565339966 abstract "Universal testing for Lynch syndrome is now a routine component of the diagnostic work-up of endometrial cancer patients. The purpose of this study was to identify prospectively the barriers to universal screening based on a tissue testing approach [microsatellite instability (MSI) analysis, IHC for DNA mismatch repair proteins, and MLH1 methylation analysis]. Endometrial carcinoma patients (n = 213) prospectively underwent microsatellite instability and IHC testing for expression of DNA mismatch repair (MMR) proteins. Patients with low (MSI-L) or high (MSI-H) levels of tumor MSI or immunohistochemical loss of MLH1 (and absent MLH1 methylation), MSH2, MSH6, or PMS2 were referred to a genetic counselor for consideration of germline testing. Six discordances (3.1% of tested cases) between IHC and MSI were identified. Half of these exhibited heterogeneous immunohistochemical loss of MLH1/PMS2 and were microsatellite stable (MSS). Of the remaining cases, one was MSS with immunohistochemical loss of MSH6, one was MSS with immunohistochemical loss of MLH1/PMS2 and absent MLH1 promoter methylation, and one was MSI-H with intact expression of DNA MMR proteins. Four patients had MSI-L tumors with intact immunohistochemical protein expression; the clinical significance of MSI-L in endometrial cancer is unclear. Eight patients did not have germline mutations despite tissue testing suggesting Lynch syndrome. Including cases with insufficient tissue for testing and patients declining tissue or germline testing, we encountered significant barriers to universal screening in 13.6% of screened patients (29/213) that preclude designation of a tumor as sporadic or hereditary. Cancer Prev Res; 10(2); 108-15. ©2016 AACR." @default.
• W2565339966 created "2017-01-06" @default.
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• W2565339966 date "2017-02-01" @default.
• W2565339966 modified "2023-10-16" @default.
• W2565339966 title "Clinical Challenges Associated with Universal Screening for Lynch Syndrome–Associated Endometrial Cancer" @default.
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• W2565339966 doi "https://doi.org/10.1158/1940-6207.capr-16-0219" @default.
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