Universal tumor screening in a population with MSH6- and PMS2-associated Lynch syndrome

被引：3

作者：

Einarsson, Haukur ^{[1
]}

Runarsdottir, Johanna Run ^{[2
]}

Tryggvason, Thordur ^{[1
]}

Snaebjornsson, Petur ^{[3
]}

Smaradottir, Agnes ^{[4
]}

Stefansdottir, Vigdis ^{[5
]}

Thoroddsen, Asgeir ^{[6
]}

Arngrimsson, Reynir ^{[5
,7
]}

Jonasson, Jon Gunnlaugur ^{[1
,7
]}

Haraldsdottir, Sigurdis ^{[4
,7
]}

机构：

[1] Landspitali Univ Hosp Iceland, Dept Pathol, Reykjavik, Iceland

[2] Landspitali Univ Hosp Iceland, Dept Internal Med, Reykjavik, Iceland

[3] Netherlands Canc Inst, Dept Pathol, Amsterdam, Netherlands

[4] Landspitali Univ Hosp Iceland, Dept Oncol, Reykjavik, Iceland

[5] Landspitali Univ Hosp Iceland, Dept Genet & Mol Med, Reykjavik, Iceland

[6] Landspitali Univ Hosp Iceland, Dept Obstet & Gynecol, Reykjavik, Iceland

[7] Univ Iceland, Fac Med, Reykjavik, Iceland

来源：

GENETICS IN MEDICINE | 2022年 / 24卷 / 05期

关键词：

Colorectal carcinoma; Endometrial carcinoma; Genetic counseling; MMR deficient; MMR proficient; NONPOLYPOSIS COLORECTAL-CANCER; MISMATCH REPAIR; ENDOMETRIAL CANCER; MICROSATELLITE INSTABILITY; MANAGEMENT; FEASIBILITY; MLH1;

D O I：

10.1016/j.gim.2022.01.012

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Purpose: Universal screening for Lynch syndrome (LS) on resected colorectal carcinomas (CRCs) and endometrial carcinomas (ECs) was implemented in Iceland in 2017 using immunohistochemistry (IHC) for mismatch repair (MMR) proteins. We examined the efficacy of the universal screening algorithm to detect LS and the diagnostic accuracy of MMR IHC by comparing results with a population-based genotype database. Methods: All patients diagnosed with CRC or EC per the Icelandic Cancer Registry from 2017 to 2019 who had tumor MMR IHC performed were included. Pathology reports and patient charts were reviewed. MMR IHC stains were crossmatched with genotyping results obtained from the deCODE database. Results: IHC staining was done on 404 patients with CRC and 74 patients with EC. A total of 61 (15.1%) patients with CRC and 15 (20.3%) patients with EC were MMR-deficient. MMR IHC had 88.9% sensitivity in identifying patients with LS and a positive predictive value of 10.7%. Only 50% of individuals were appropriately referred for genetic testing, leading to underdiagnosis of LS. Conclusion: Universal screening for LS using MMR protein IHC in CRC and EC accurately identified patients appropriate for genetic testing in a population with MSH6 and PMS2 LS predominance. Because of lack of referral to genetic counseling, only 50% of patients with LS were identified through the screening algorithm. (C) 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.

引用

页码：999 / 1007

页数：9

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