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  • Title: Comparison of clinical schemas and morphologic features in predicting Lynch syndrome in mutation-positive patients with endometrial cancer encountered in the context of familial gastrointestinal cancer registries.
    Author: Ryan P, Mulligan AM, Aronson M, Ferguson SE, Bapat B, Semotiuk K, Holter S, Kwon J, Kalloger SE, Gilks CB, Gallinger S, Pollett A, Clarke BA.
    Journal: Cancer; 2012 Feb 01; 118(3):681-8. PubMed ID: 21721000.
    Abstract:
    BACKGROUND: Endometrial cancer (EC) is the most common extraintestinal malignancy in Lynch syndrome (LS) and often is the sentinel malignancy, yet there is no consensus regarding LS-EC detection algorithms. In this study, the authors determined the efficacy of family/personal history and tumor morphology in predicting LS in a cohort of patients with EC who had mutation-proven LS. METHODS: Amsterdam II (AmII) criteria, revised Bethesda guidelines (rBG), and Society of Gynecologic Oncologists (SGO) clinical screening criteria were applied to the pedigrees of 76 patients with mutation-proven LS who had pathology-proven EC. When tumors were tested for microsatellite instability (MSI) phenotype status or mismatch-repair protein-immunohistochemical (MMR-IHC) expression, those results also were reviewed, and LS-associated histopathologic features were documented in 38 available patients. RESULTS: Of 76 patients, 36%, 58%, 71%, and 93% would have been selected for further testing for LS by pedigree screening at the time of EC diagnosis with rBG, AmII, SGO 20%-to-25%, and SGO 5%-to-10% criteria, respectively. Ninety percent (18 of 20 tumors) of tested ECs had high MSI, and 96% (22 of 23 tumors) had abnormal MMR-IHC expression. At least 1 LS-EC morphologic feature was present in 16 of 38 tumors (42%). CONCLUSIONS: Clinical screening criteria had variable efficacy for the identification of LS-associated EC, and SGO 5%-to-10% criteria performed best. Characteristic pathologic features were present in a minority of patients. Although a high proportion of LS-ECs had the MSI phenotype and were MMR deficient, the specificity of these tests and of clinical screening for LS in unselected patients with EC has been poorly described. Prospective studies to determine the optimal combination of these screening modalities are required.
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