Lynch syndrome among gynecologic oncology patients meeting Bethesda guidelines for screening.
Lynch syndrome among gynecologic oncology patients meeting Bethesda guidelines for screening.
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DOI：
10.1016/j.ygyno.2009.11.021
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发表时间：
2010-03
影响因子：
4.7
通讯作者：
Karlan, Beth Y.
中科院分区：
文献类型：
--
作者：
Walsh, Christine S.;Blum, Audra;Walts, Ann;Alsabeh, Randa;Tran, Hang;Koeffler, H. Phillip;Karlan, Beth Y.
关键词：
林奇综合征（LS）的特征是结直肠癌和子宫内膜癌和卵巢癌等妇科恶性肿瘤的终生发病率很高。LS家族的鉴定是重要的，因为它允许提高癌症筛查，降低结直肠癌死亡率。最初的1996年Bethesda指南包括两个妇科人群，应进一步评估LS：45岁之前患有子宫内膜癌的人群和患有两种LS相关癌症的人群（即同时发生子宫内膜癌和卵巢癌）。我们的研究旨在估计LS在这两个人群中的患病率。我们利用了一种诊断算法，包括免疫组化错配修复蛋白表达，然后选择性评价微卫星不稳定性和MLH 1基因启动子甲基化。在72例符合条件的患者中，9例（12%）具有与LS一致的分子结果：早发性子宫内膜癌组中6/50（12%），同步原发癌组中3/22（14%）。在另外3例病例中，MLH 1沉默是由于启动子甲基化：早发性子宫内膜癌组中1/50（2%），同步原发癌组中2/22（9%）。在9名分子标准提示LS的女性中，只有3名具有符合阿姆斯特丹标准的谱系。诊断算法可以识别LS患者和需要进一步基因检测的患者。我们的研究结果加强了对45岁以前诊断为子宫内膜癌的妇女和同时患有子宫内膜癌和卵巢癌的妇女进行LS筛查的建议，无论其家族史如何。
Lynch Syndrome (LS) is characterized by a high lifetime incidence of colorectal cancer and gynecologic malignancies such as endometrial and ovarian cancer. Identification of LS families is important as it allows for heightened cancer screening which decreases colorectal cancer mortality. The original 1996 Bethesda guidelines included two gynecologic populations that should be further evaluated for LS: those with endometrial cancer before the age of 45 and those with two LS-related cancers (i.e. synchronous endometrial and ovarian cancer). Our study aims to estimate the prevalence of LS in these two populations. We utilized a diagnostic algorithm that included immunohistochemistry for mismatch repair protein expression followed by selective evaluation for microsatellite instability and MLH1 gene promoter methylation. Among 72 eligible patients, 9 (12%) had molecular findings consistent with LS: 6/50 (12%) in the early-onset endometrial cancer group and 3/22 (14%) in the synchronous primary cancer group. In an additional 3 cases, MLH1 silencing was due to promoter methylation: 1/50 (2%) in the early-onset endometrial cancer group and 2/22 (9%) in the synchronous primary cancer group. Of the 9 women with molecular criteria suggesting LS, only three had pedigrees meeting the Amsterdam criteria. A diagnostic algorithm can identify patients with LS and those who warrant further genetic testing. Our findings reinforce the recommendation that women diagnosed with endometrial cancer before age 45 and women with synchronous endometrial and ovarian cancer be screened for LS, irrespective of family history.
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影响因子：
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