JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., EXTRAMURAL
Add like
Add dislike
Add to saved papers

Screening for germline mismatch repair mutations following diagnosis of sebaceous neoplasm.

JAMA Dermatology 2014 December
IMPORTANCE Sebaceous neoplasms (SNs) define the Muir-Torre syndrome variant of Lynch syndrome (LS), which is associated with increased risk for colon and other cancers necessitating earlier and more frequent screening to reduce morbidity and mortality.Immunohistochemical (IHC) staining for mismatch repair (MMR) proteins in SNs can be used to screen for LS, but data on subsequent germline genetic testing to confirm LS diagnosis are limited.OBJECTIVE To characterize the utility of IHC screening of SNs in identification of germline MMR mutations confirming LS.DESIGN, SETTING, AND PARTICIPANTS Retrospective study at 2 academic cancer centers of 86 adult patients referred for clinical genetics evaluation after diagnosis of SN.MAIN OUTCOMES AND MEASURES Results of tumor IHC testing and germline genetic testing were reviewed to determine positive predictive value and sensitivity of IHC testing in diagnosis of LS. Clinical variables, including age at diagnosis of SN, clinical diagnostic criteria for LS and Muir-Torre syndrome, and family history characteristics were compared between mutation carriers and noncarriers.RESULTS Of 86 patients with SNs, 25 (29%) had germline MMR mutations confirming LS.Among 77 patients with IHC testing on SNs, 38 (49%) had loss of staining of 1 or more MMR proteins and 14 had germline MMR mutations. Immunohistochemical analysis correctly identified 13 of 16 MMR mutation carriers, corresponding to 81% sensitivity. Ten of 12 patients(83%) with more than 1 SN had MMR mutations. Fifty-two percent of MMR mutation carriers did not meet clinical diagnostic criteria for LS, and 11 of 25 (44%) did not meet the clinical definition of Muir-Torre syndrome. CONCLUSIONS AND RELEVANCE Immunohistochemical screening of SNs is effective in identifying patients with germline MMR mutations and can be used as a first-line test when LSis suspected. Abnormal IHC results, including absence of MSH2, are not diagnostic of LS and should be interpreted cautiously in conjunction with family history and germline genetic testing. Use of family history to select patients for IHC screening has substantial limitations,suggesting that universal IHC screening of SNs merits further study. Clinical genetics evaluation is warranted for patients with abnormal IHC test results, normal IHC test results with personal or family history of other LS-associated neoplasms, and/or multiple SNs.

Full text links

For the best experience, use the Read mobile app

Group 7SearchHeart failure treatmentPapersTopicsCollectionsEffects of Sodium-Glucose Cotransporter 2 Inhibitors for the Treatment of Patients With Heart Failure Importance: Only 1 class of glucose-lowering agents-sodium-glucose cotransporter 2 (SGLT2) inhibitors-has been reported to decrease the risk of cardiovascular events primarily by reducingSeptember 1, 2017: JAMA CardiologyAssociations of albuminuria in patients with chronic heart failure: findings in the ALiskiren Observation of heart Failure Treatment study.CONCLUSIONS: Increased UACR is common in patients with heart failure, including non-diabetics. Urinary albumin creatininineJul, 2011: European Journal of Heart FailureRandomized Controlled TrialEffects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.Review

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

Read by QxMD is copyright © 2021 QxMD Software Inc. All rights reserved. By using this service, you agree to our terms of use and privacy policy.

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app