Identifying patients with Lynch syndrome using a universal tumor screening program in an integrated healthcare system.
Identifying patients with Lynch syndrome using a universal tumor screening program in an integrated healthcare system.
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使用综合医疗保健系统中的通用肿瘤筛查程序鉴定患有林奇综合征的患者。
DOI：
10.1186/s13053-022-00217-1
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发表时间：
2022-04-18
影响因子：
1.7
通讯作者：
Hunter, Jessica Ezzell
中科院分区：
文献类型：
--
作者：
Crain, Philip R.;Zepp, Jamilyn M.;Gille, Sara;Jenkins, Lindsay;Kauffman, Tia L.;Shuster, Elizabeth;Goddard, Katrina A. B.;Wilfond, Benjamin S.;Hunter, Jessica Ezzell
Lynch综合征（LS）与结直肠癌（CRC）和子宫内膜癌（EC）的风险增加有关。建议对所有诊断为CRC和EC的个体进行通用肿瘤筛查（UTS），以增加LS的识别。Kaiser Permanente Northwest（KPNW）在2016年1月和2016年11月新诊断为CRC和EC的个体中实施了LS的UTS计划。KPNW的UTS从肿瘤组织的免疫组织化学（IHC）开始，以确定与LS相关的错配修复蛋白（MLH 1，MSH 2，MSH 6和PMS 2）的丢失。在显示MLH 1缺失的IHC之后进行反射测试（自动测试），以检测BRAF V600 E变体（在CRC的情况下）和MLH 1启动子超甲基化的存在，以排除可能的散发病例。新诊断为CRC和EC的个体是在各自的UTS计划开始至2018年7月之间确定的。对电子病历进行了审查，以提取与UTS相关的患者数据，包括IHC和反射检测结果、转诊至遗传科的日期以及LS的生殖系基因检测结果。362名诊断为CRC的个体中的313名和64名诊断为EC的个体中的61名通过IHC筛查LS。大多数（47/52或90%，包括46/49 CRC和1/3 EC）未通过IHC筛查的个体仅具有可用的活检样本。14人（3.7%，包括13/313 CRC和1/61 EC）在反射测试后收到异常结果，并被转介进行遗传咨询。其中，10名个体（总体占71%，包括9/13名CRC和1/1名EC）接受了LS的生殖系基因检测。发现5名被诊断患有CRC的个体具有致病性变体。在PMS 2（n = 3）、MLH 1（n = 1）和MSH 6（n = 1）中。在诊断为EC的个体中未发现致病性变异。UTS确定了存在LS风险的个体。大多数筛查为LS阳性的个体进行了LS的后续生殖系基因检测。活检样本的一致使用是改善UTS的机会。
Lynch syndrome (LS) is associated with an increased risk of colorectal (CRC) and endometrial (EC) cancers. Universal tumor screening (UTS) of all individuals diagnosed with CRC and EC is recommended to increase identification of LS. Kaiser Permanente Northwest (KPNW) implemented a UTS program for LS among individuals newly diagnosed with CRC in January 2016 and EC in November 2016. UTS at KPNW begins with immunohistochemistry (IHC) of tumor tissue to determine loss of mismatch repair proteins associated with LS (MLH1, MSH2, MSH6, and PMS2)., IHC showing loss of MLH1 is followed by reflex testing (automatic testing) to detect the presence of the BRAF V600E variant (in cases of CRC) and MLH1 promoter hypermethylation to rule out likely sporadic cases. Individuals newly diagnosed with CRC and EC were identified between the initiation of the respective UTS programs and July 2018. Electronic medical records were reviewed to extract patient data related to UTS, including IHC and reflex testing results, date of referrals to the genetics department, and results of germline genetic testing for LS. 313 out of 362 individuals diagnosed with CRC and 61 out of 64 individuals diagnosed with EC who were eligible were screened by IHC for LS. Most (47/52 or 90%, including 46/49 CRC and 1/3 EC) individuals that were not screened by IHC only had a biopsy sample available. Fourteen individuals (3.7% overall, including 13/313 CRC and 1/61 EC) received an abnormal result after reflex testing and were referred for genetic counseling. Of these, 10 individuals (71% overall, including 9/13 CRC and 1/1 EC) underwent germline genetic testing for LS. Five individuals diagnosed with CRC were found to have pathogenic variants. in PMS2 (n = 3), MLH1 (n = 1), and MSH6 (n = 1). No pathogenic variants were identified in individuals diagnosed with EC. UTS identified individuals at risk for LS. Most individuals who screened positive for LS had follow-up germline genetic testing for LS. The consistent use of biopsy samples is an opportunity to improve UTS.
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DOI：
10.1038/gim.2013.43
发表时间：
2013-12
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1016/j.cgh.2018.08.038
发表时间：
2018-12
期刊：
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
影响因子：
--
作者：
Muller C;Lee SM;Barge W;Siddique SM;Berera S;Wideroff G;Tondon R;Chang J;Peterson M;Stoll J;Katona BW;Sussman DA;Melson J;Kupfer SS
通讯作者：
Kupfer SS
影响因子：
7.2
作者：
通讯作者：
--
影响因子：
2.2
作者：
Barrow, Emma;Hill, James;Evans, D. Gareth
通讯作者：
Evans, D. Gareth
影响因子：
158.5
作者：
Hampel, H;Frankel, WL;Papadopoulos, N
通讯作者：
Papadopoulos, N