Universal Screening for Mismatch-Repair Deficiency in Endometrial Cancers to Identify Patients With Lynch Syndrome and Lynch-like Syndrome
Universal Screening for Mismatch-Repair Deficiency in Endometrial Cancers to Identify Patients With Lynch Syndrome and Lynch-like Syndrome
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DOI：
10.1097/pgp.0000000000000312
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发表时间：
2017-03-01
影响因子：
2.4
通讯作者：
Howitt, Brooke E.
中科院分区：
文献类型：
--
作者：
Watkins, Jaclyn C.;Yang, Eric J.;Howitt, Brooke E.
虽然尚未达成共识的普遍错配修复（MMR）蛋白免疫组化（IHC）筛查林奇综合征（LS）在子宫内膜癌（EC），越来越多的机构已采用通用的筛查协议类似于那些用于结直肠癌。在这里，我们描述了我们的机构的经验与前瞻性的通用筛选方案，其中所有的EC切除超过19个月（n = 242）进行筛选MLH1，PMS2，MSH2和MSH6的缺陷，使用IHC，随后MLH1启动子甲基化测试时，适当的。在获得同意后，肿瘤样本进行下一代测序。通过IHC筛查共确定了11例未甲基化的MMR缺陷病例（占队列的4.5%）。在10例病例中进行了生殖系检测，并在4例患者（队列的1.7%）中证实了LS。在我们的4例确诊LS病例中，1例不符合传统LS筛选标准（例如，年龄低于50岁，修订的Bethesda标准）。此外，普遍筛查确定了6例生殖细胞阴性的MMR缺陷非甲基化病例，其中4例发生在50岁以上的女性中。尽管我们的下一代测序数据表明其中4例存在体细胞突变，但这些病例可能代表“林奇样综合征”病例。我们的结论是，使用传统的筛查指南可能会遗漏一部分LS病例。筛查Lynch样综合征的价值尚未确定。虽然在EC的普遍筛查的成本效益尚未得到阐明，我们得出结论，普遍的IHC筛查是目前一个合理的，可以说是上级，LS筛查的方法。
Although consensus has yet to be reached on universal mismatch-repair (MMR) protein immunohistochemical (IHC) screening for Lynch syndrome (LS) in endometrial cancer (EC), an increasing number of institutions have adopted universal screening protocols similar to those used for colorectal carcinoma. Here we describe our institution's experience with a prospective universal screening protocol in which all ECs resected over a period of 19 months (n = 242) were screened for MLH1, PMS2, MSH2, and MSH6 deficiencies using IHC, followed by MLH1 promoter methylation testing when appropriate. When consent was obtained, tumor samples underwent next-generation sequencing. A total of 11 unmethylated MMR-deficient cases (4.5% of cohort) were identified through IHC screening. Germline testing was performed in 10 cases and confirmed LS in 4 patients (1.7% of cohort). Of our 4 confirmed LS cases, 1 did not meet traditional LS screening criteria (eg, age below 50 y, Revised Bethesda criteria). In addition, universal screening identified 6 germline-negative MMR-deficient nonmethylated cases, 4 of which occurred in women older than 50. Although our next-generation sequencing data suggest somatic mutations in 4 of these cases, it is possible that these cases may represent cases of "Lynch-like syndrome.'' We conclude that a subset of LS cases could be missed using traditional screening guidelines. The value of screening for Lynch-like syndrome has yet to be determined. Although the cost-effectiveness of universal screening in EC has yet to be elucidated, we conclude that universal IHC screening is currently a reasonable, and arguably superior, approach to screening for LS.