Universal Screening of Both Endometrial and Colon Cancers Increases the Detection of Lynch Syndrome
Universal Screening of Both Endometrial and Colon Cancers Increases the Detection of Lynch Syndrome
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DOI：
10.1002/cncr.31534
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发表时间：
2018-08-01
期刊：
影响因子：
6.2
通讯作者：
Chung, Daniel C.
中科院分区：
文献类型：
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作者：
Adar, Tomer;Rodgers, Linda H.;Chung, Daniel C.
背景：Lynch综合征（LS）是结直肠癌（CRC）和子宫内膜癌（EC）最常见的遗传性病因。目前建议对所有CRC进行LS筛查，但对EC的筛查不一致。本研究的目的是确定在同一人群中筛查CRC和EC肿瘤的附加值。方法：分别于2011年和2013年在2家中心（一级和三级）启动了针对所有新诊断CRC和EC患者的前瞻性、基于免疫组织化学（IHC）的筛查项目。建议对mutS同源物2（MSH 2）、MSH 6或减数分裂后分离增加2（PMS 2）表达缺失的肿瘤患者以及mutL同源物1（MLH 1）表达缺失且无v-Raf小鼠肉瘤病毒癌基因同源物B（BRAF）突变或MLH 1启动子甲基化的肿瘤患者进行基因检测。确定LS患者的Amsterdam II标准、修订的Bethesda标准和基因突变预测模型（PREMM 1、2、6和PREMM 5预测模型）评分。研究结果：总共有1290名CRC患者和484名EC患者接受了LS筛查，分别推荐137名患者（10.6%）和32名患者（6.6%）进行基因检测（P= 0.01）。在16例CRC患者（1.2%）和8例EC患者（1.7%）中确定了LS。在推荐进行基因检测的患者中，EC患者的LS诊断率较高（25.0% vs 11.7%，P= 0.052）。Amsterdam II标准、修订的Bethesda标准和两种PREMM计算器分别会遗漏62.5%、50.0%和12.5%的LS患者。结论：扩大LS的通用筛查计划，以纳入EC患者，这些患者中有50%以上的LS患者被确定，其中许多患者可能被风险评估工具（包括PREMM 5）遗漏。LS的普遍筛查项目应包括CRC和EC。(C)2018美国癌症协会
BACKGROUND: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC) and endometrial cancer (EC). Screening of all CRCs for LS is currently recommended, but screening of ECs is inconsistent. The objective of this study was to determine the added value of screening both CRC and EC tumors in the same population. METHODS: A prospective, immunohistochemistry (IHC)-based screening program for all patients with newly diagnosed CRCs and ECs was initiated in 2011 and 2013, respectively, at 2 centers (primary and tertiary). Genetic testing was recommended for those who had tumors with absent mutS homolog 2 (MSH2), MSH6, or postmeiotoic segregation increased 2 (PMS2) expression and for those who had tumors with absent mutL homolog 1 (MLH1) expression and no v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation or MLH1 promoter methylation. Amsterdam II criteria, revised Bethesda criteria, and scores from prediction models for gene mutations (the PREMM1,2,6 and PREMM5 prediction models) were ascertained in patients with LS. RESULTS: In total, 1290 patients with CRC and 484 with EC were screened for LS, and genetic testing was recommended for 137 patients (10.6%) and 32 patients (6.6%), respectively (P=.01). LS was identified in 16 patients (1.2%) with CRC and in 8 patients (1.7%) with EC. Among patients for whom genetic testing was recommended, the LS diagnosis rate was higher among those with EC (25.0% vs 11.7%, P=.052). The Amsterdam II criteria, revised Bethesda criteria, and both PREMM calculators would have missed 62.5%, 50.0%, and 12.5% of the identified patients with LS, respectively. CONCLUSIONS: Expanding a universal screening program for LS to include patients who had EC identified 50% more patients with LS, and many of these patients would have been missed by risk assessment tools (including PREMM5). Universal screening programs for LS should include both CRC and EC. (C) 2018 American Cancer Society.