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Universal screening for Lynch syndrome in endometrial cancers: frequency of germline mutations and identification of patients with Lynch-like syndrome.
Hum Pathol. 2017 12; 70:121-128.HP

Abstract

Lynch syndrome (LS) is an inherited clinical syndrome characterized by a high risk of colorectal, endometrial (lifetime risk of up to 60%), ovarian, and urinary tract cancers. The diagnosis is confirmed by identification of germline mutations in the DNA mismatch repair genes MLH1, PMS2, MSH2, MSH6, or EPCAM. In 2015, our institution implemented universal screening of endometrial cancer (EC) hysterectomy specimens by mismatch repair immunohistochemistry (IHC) with reflex MLH1 promoter hypermethylation analysis for tumors with loss of MLH1/PMS2 expression. Patients with tumors negative for MLH1 methylation and those with a loss of the heterodimer pair MSH2 and MSH6, or isolated loss of either PMS2 or MSH6 were referred to the Familial Cancer Program for genetic counseling and consideration of germline testing. Between May 2015 to Dec 2016, 233 EC patients were screened by IHC for LS with a median age of 63 years. Sixty tumors (27%) had abnormal IHC staining results. Fifty-one (22%) harbored heterodimeric loss of MLH1 and PMS2, 49 of which showed MLH1 promoter methylation (1 failure, 1 negative). One showed loss of MLH1/PMS2 and MSH6, 2 showed loss of MSH2/MSH6, and 6 had isolated loss of MSH6 only. Ten patients underwent genetic counseling, and germline testing was performed in 8; LS was confirmed in 5 patients (2.1%). In addition, 3 patients with negative germline testing and presumed Lynch-like syndrome were identified and offered additional somatic testing. Universal screening for LS in EC patients has yielded positive results for identification of patients at risk for this inherited syndrome.

Authors+Show Affiliations

Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH.Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH; The Geisel School of Medicine at Dartmouth, Hanover, NH, 03755.Department of Obstetrics and Gynecology, Dartmouth-Hitchcock Medical Center, Lebanon, NH; The Geisel School of Medicine at Dartmouth, Hanover, NH, 03755.Familial Cancer Program, Dartmouth-Hitchcock Medical Center, Lebanon, NH.Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH; The Geisel School of Medicine at Dartmouth, Hanover, NH, 03755; Norris Cotton Cancer Center, Lebanon, NH, 03756. Electronic address: Laura.J.Tafe@hitchcock.org.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29107668

Citation

Dillon, Jessica L., et al. "Universal Screening for Lynch Syndrome in Endometrial Cancers: Frequency of Germline Mutations and Identification of Patients With Lynch-like Syndrome." Human Pathology, vol. 70, 2017, pp. 121-128.
Dillon JL, Gonzalez JL, DeMars L, et al. Universal screening for Lynch syndrome in endometrial cancers: frequency of germline mutations and identification of patients with Lynch-like syndrome. Hum Pathol. 2017;70:121-128.
Dillon, J. L., Gonzalez, J. L., DeMars, L., Bloch, K. J., & Tafe, L. J. (2017). Universal screening for Lynch syndrome in endometrial cancers: frequency of germline mutations and identification of patients with Lynch-like syndrome. Human Pathology, 70, 121-128. https://doi.org/10.1016/j.humpath.2017.10.022
Dillon JL, et al. Universal Screening for Lynch Syndrome in Endometrial Cancers: Frequency of Germline Mutations and Identification of Patients With Lynch-like Syndrome. Hum Pathol. 2017;70:121-128. PubMed PMID: 29107668.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Universal screening for Lynch syndrome in endometrial cancers: frequency of germline mutations and identification of patients with Lynch-like syndrome. AU - Dillon,Jessica L, AU - Gonzalez,Jorge L, AU - DeMars,Leslie, AU - Bloch,Katarzyna J, AU - Tafe,Laura J, Y1 - 2017/10/28/ PY - 2017/07/17/received PY - 2017/10/17/revised PY - 2017/10/18/accepted PY - 2017/11/7/pubmed PY - 2018/10/16/medline PY - 2017/11/7/entrez KW - Endometrial carcinoma KW - Germline KW - Lynch syndrome KW - Lynch-like syndrome KW - Mismatch repair SP - 121 EP - 128 JF - Human pathology JO - Hum Pathol VL - 70 N2 - Lynch syndrome (LS) is an inherited clinical syndrome characterized by a high risk of colorectal, endometrial (lifetime risk of up to 60%), ovarian, and urinary tract cancers. The diagnosis is confirmed by identification of germline mutations in the DNA mismatch repair genes MLH1, PMS2, MSH2, MSH6, or EPCAM. In 2015, our institution implemented universal screening of endometrial cancer (EC) hysterectomy specimens by mismatch repair immunohistochemistry (IHC) with reflex MLH1 promoter hypermethylation analysis for tumors with loss of MLH1/PMS2 expression. Patients with tumors negative for MLH1 methylation and those with a loss of the heterodimer pair MSH2 and MSH6, or isolated loss of either PMS2 or MSH6 were referred to the Familial Cancer Program for genetic counseling and consideration of germline testing. Between May 2015 to Dec 2016, 233 EC patients were screened by IHC for LS with a median age of 63 years. Sixty tumors (27%) had abnormal IHC staining results. Fifty-one (22%) harbored heterodimeric loss of MLH1 and PMS2, 49 of which showed MLH1 promoter methylation (1 failure, 1 negative). One showed loss of MLH1/PMS2 and MSH6, 2 showed loss of MSH2/MSH6, and 6 had isolated loss of MSH6 only. Ten patients underwent genetic counseling, and germline testing was performed in 8; LS was confirmed in 5 patients (2.1%). In addition, 3 patients with negative germline testing and presumed Lynch-like syndrome were identified and offered additional somatic testing. Universal screening for LS in EC patients has yielded positive results for identification of patients at risk for this inherited syndrome. SN - 1532-8392 UR - https://www.unboundmedicine.com/medline/citation/29107668/Universal_screening_for_Lynch_syndrome_in_endometrial_cancers:_frequency_of_germline_mutations_and_identification_of_patients_with_Lynch_like_syndrome_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0046-8177(17)30391-X DB - PRIME DP - Unbound Medicine ER -