Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients
Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients
复制标题
DOI：
10.1158/0008-5472.can-06-1114
复制
发表时间：
2006-08-01
期刊：
影响因子：
11.2
通讯作者：
de la Chapelle, Albert
中科院分区：
文献类型：
--
作者：
Hampel, Heather;Frankel, Wendy;de la Chapelle, Albert
子宫内膜癌是患有林奇综合征的女性中最常见的癌症。确认患有林奇综合征的个体是可取的，因为他们可以从增加的癌症监测中受益。本研究的目的是确定在所有子宫内膜癌患者中进行Lynch综合征分子筛查的可行性和可取性。未经选择的子宫内膜癌患者(N=543例)。所有肿瘤均接受微卫星不稳定性(NISI)检测。对MSI阳性肿瘤患者进行了MLH1、MSH2、MSH6和PMS2的胚系突变检测。在所研究的543个肿瘤中，118个(21.7%)为MSI阳性(其中98个为高MSI，20个为低MSI)。所有118例MSI阳性肿瘤患者都进行了突变检测，其中9人有有害的生殖系突变(1例MLH1，3例MSH2，5例MSH6)。此外，一例MSI阴性肿瘤的MSH6免疫组织化学染色异常，随后发现MSH6发生突变。免疫组织化学染色在所有7例截断突变阳性病例中与突变结果一致，但在3例错义突变病例中有2例不一致。我们得出结论，在俄亥俄州中部，至少1.8%(95%可信区间，0.9-3.5%)的新诊断子宫内膜癌患者患有林奇综合征。10名林奇综合征患者中有7名不符合任何已发表的遗传性非息肉病性结直肠癌诊断标准，其中6名患者在50岁时被确诊。对所有子宫内膜癌患者进行Lynch综合征的研究是可行的，也可能是可取的，使用MSI和免疫组织化学相结合的分子预筛选，然后进行基因测序和缺失分析。
Endometrial cancer is the most common cancer in women with Lynch syndrome. The identification of individuals with Lynch syndrome is desirable because they can benefit from increased cancer surveillance. The purpose of this study was to determine the feasibility and desirability of molecular screening for Lynch syndrome in all endometrial cancer patients. Unselected endometrial cancer patients (N = 543) were studied. All tumors underwent microsatellite instability (NISI) testing. Patients with MSI-positive tumors underwent testing for germ line mutations in MLH1, MSH2, MSH6, and PMS2. Of 543 tumors studied, 118 (21.7%) were MSI positive (98 of 118 MSI high and 20 of 118 MSI low). All 118 patients with MSI-positive tumors had mutation testing, and nine of them had deleterious germ line mutations (one MLH1, three MSH2, and five MSH6). In addition, one case with an MSI-negative tumor had abnormal MSH6 immunohistochemical staining and was subsequently found to have a mutation in MSH6. Immunohistochemical staining was consistent with the mutation result in all seven truncating mutation-positive cases but was not consistent in two of the three missense mutation cases. We conclude that in central Ohio, at least 1.8% (95% confidence interval, 0.9-3.5%) of newly diagnosed endometrial cancer patients had Lynch syndrome. Seven of the 10 Lynch syndrome patients did not meet any published criteria for hereditary nonpolyposis colorectal cancer, and six of them were diagnosed at age > 50. Studying all endometrial cancer patients for Lynch syndrome using a combination of MSI and immunohistochemistry for molecular prescreening followed by gene sequencing and deletion analysis is feasible and may be desirable.