Evaluation of Clinical Criteria for the Identification of Lynch Syndrome among Unselected Patients with Endometrial Cancer
Evaluation of Clinical Criteria for the Identification of Lynch Syndrome among Unselected Patients with Endometrial Cancer
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DOI：
10.1158/1940-6207.capr-13-0359
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发表时间：
2014-07-01
影响因子：
3.3
通讯作者：
Broaddus, Russell R.
中科院分区：
文献类型：
--
作者：
Bruegl, Amanda S.;Djordjevic, Bojana;Broaddus, Russell R.
临床标准，主要是年轻的癌症发病年龄和标志性癌症的家族史，已被开发用于识别林奇综合征风险升高的个体，目的是早期识别和癌症预防。2007年，妇科肿瘤学会（SGO）编纂了妇科癌症女性的标准。这些标准尚未在基于人口的环境中得到验证。对412例子宫内膜癌患者进行DNA错配修复蛋白免疫组化表达和MLH 1甲基化评估，以将肿瘤分类为散发性或可能的Lynch综合征（PLS）。在该队列中，10.5%的患者基于肿瘤检测被指定为PLS。SGO标准识别这些相同病例的灵敏度和特异性分别为32.6% [95%置信区间（CI），19.2-48.5]和77%（95% CI，72.7-81.8）。除了子宫下段的肿瘤位置外，临床特征、家族史和病理变量的多变量分析未能确定散发性和PLS组之间的显著差异。一项简化的成本效益分析表明，SGO临床标准和通用组织检测策略的PLS患者人均成本相当。总之，SGO标准成功地识别了年轻或有显著标志性肿瘤家族史的子宫内膜癌妇女中的PLS病例。然而，更大比例的PLS患者年龄较大，家族史不太明显，这种筛查策略没有检测到。通用组织测试可能是必要的，以捕捉更多的个人在风险有林奇综合征。（C）2014年AACR。
Clinical criteria, primarily young age of cancer onset and family history of signature cancers, have been developed to identify individuals at elevated risk for Lynch syndrome with the goals of early identification and cancer prevention. In 2007, the Society of Gynecologic Oncology (SGO)-codified criteria for women presenting with gynecologic cancers. These criteria have not been validated in a population-based setting. For 412 unselected endometrial cancers, immunohistochemical expression of DNA mismatch repair proteins and MLH1 methylation were assessed to classify tumors as sporadic or probable Lynch syndrome (PLS). In this cohort, 10.5% of patients were designated as PLS based on tumor testing. The sensitivity and specificity of the SGO criteria to identify these same cases were 32.6% [95% confidence interval (CI), 19.2-48.5] and 77% (95% CI, 72.7-81.8), respectively. With the exception of tumor location in the lower uterine segment, multivariate analysis of clinical features, family history, and pathologic variables failed to identify significant differences between the sporadic and PLS groups. A simplified cost-effectiveness analysis demonstrated that the SGO clinical criteria and universal tissue testing strategies had comparable costs per patient with PLS identified. In conclusion, the SGO criteria successfully identify PLS cases among women with endometrial cancer who are young or have significant family history of signature tumors. However, a larger proportion of patients with PLS who are older and have less significant family history are not detected by this screening strategy. Universal tissue testing may be necessary to capture more individuals at risk for having Lynch syndrome. (C)2014 AACR.