Feasibility of Screening for Lynch Syndrome Among Patients With Colorectal Cancer
Feasibility of Screening for Lynch Syndrome Among Patients With Colorectal Cancer
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DOI：
10.1200/jco.2008.17.5950
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发表时间：
2008-12-10
影响因子：
45.3
通讯作者：
de la Chapelle, Albert
中科院分区：
文献类型：
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作者：
Hampel, Heather;Frankel, Wendy L.;de la Chapelle, Albert
目的鉴别Lynch综合征（LS）患者是非常有益的。然而，目前尚不清楚微卫星不稳定性（MSI）或免疫组织化学（IHC）是否应该作为筛查试验，以及筛查是否应该针对所有结直肠癌（CRC）患者或高危亚组患者。对500例未选择的结直肠癌患者的肿瘤进行了四种错配修复蛋白的smsi检测和免疫组化。如果MSI或IHC异常，则进行错配修复基因的完整突变分析。结果500例患者中有18例（3.6%）发生LS。18例LS患者均为高msi肿瘤（100%）；18例LS患者中17例（94%）的免疫组化预测正确。在18例先证患者中，只有8例患者（44%）的诊断年龄小于50岁，只有13例患者（72%）符合修订后的Bethesda指南。当这些结果与先前研究的1066例患者的数据相加时，整个研究队列（N = 1566）显示，1566例患者中有44例LS的总体患病率（2.8%;95% CI， 2.1%至3.8%）。对于每个先证者，平均有三个额外的家庭成员携带MMR突变。结论每35例结直肠癌患者中有1例患有LS，且每位患者至少有3例亲属患有LS；所有人都可以从加强癌症监测中受益。对于筛查，免疫组化几乎与MSI一样敏感，但免疫组化更容易获得，并有助于指导基因检测。将肿瘤分析局限于符合Bethesda标准的患者将无法识别28%（或四分之一）的LS病例。
PurposeIdentifying individuals with Lynch syndrome (LS) is highly beneficial. However, it is unclear whether microsatellite instability (MSI) or immunohistochemistry (IHC) should be used as the screening test and whether screening should target all patients with colorectal cancer (CRC) or those in high-risk subgroups.Patients and MethodsMSI testing and IHC for the four mismatch repair proteins was performed on 500 tumors from unselected patients with CRC. If either MSI or IHC was abnormal, complete mutation analysis for the mismatch repair genes was performed.ResultsAmong the 500 patients, 18 patients (3.6%) had LS. All 18 patients detected with LS (100%) had MSI-high tumors; 17 (94%) of 18 patients with LS were correctly predicted by IHC. Of the 18 probands, only eight patients (44%) were diagnosed at age younger than 50 years, and only 13 patients (72%) met the revised Bethesda guidelines. When these results were added to data on 1,066 previously studied patients, the entire study cohort (N = 1,566) showed an overall prevalence of 44 of 1,566 patients (2.8%; 95% CI, 2.1% to 3.8%) for LS. For each proband, on average, three additional family members carried MMR mutations.ConclusionOne of every 35 patients with CRC has LS, and each has at least three relatives with LS; all of whom can benefit from increased cancer surveillance. For screening, IHC is almost equally sensitive as MSI, but IHC is more readily available and helps to direct gene testing. Limiting tumor analysis to patients who fulfill Bethesda criteria would fail to identify 28% (or one in four) cases of LS.