Batte Brittany A L, Bruegl Amanda S, Daniels Molly S, Ring Kari L, Dempsey Katherine M, Djordjevic Bojana, Luthra Rajyalakshmi, Fellman Bryan M, Lu Karen H, Broaddus Russell R
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Pathology and Laboratory Medicine, University of Ottawa, The Ottawa Hospital, Ottawa, ON, Canada.
Gynecol Oncol. 2014 Aug;134(2):319-25. doi: 10.1016/j.ygyno.2014.06.009. Epub 2014 Jun 14.
Determine factors impacting the uptake of genetic counseling and results of genetic testing following universal tumor testing for Lynch syndrome in patients with endometrial cancer.
The study population consisted of two unselected cohorts of endometrial cancer patients, 408 identified retrospectively and 206 identified prospectively. Immunohistochemistry for mismatch repair protein expression and/or microsatellite instability analysis was performed on these tumors. MLH1 methylation analysis was performed on tumors with loss of MLH1 protein. Tumor studies were considered suggestive of Lynch Syndrome if they showed immunohistochemical loss of MSH2, MSH6 or PMS2, loss of MLH1 without MLH1 promoter methylation, and/or microsatellite instability. Participants with suggestive tumor studies were contacted and offered genetic counseling and testing.
In the retrospective cohort, 11% had tumor studies suggestive of Lynch syndrome, and 42% was seen for genetic counseling. A germline mutation was detected in 40%, and one had a variant of uncertain significance. In the prospective cohort, 8.7% of patients had tumor testing suggestive of Lynch syndrome; 72% were seen for genetic counseling. Germline mutations were found in 40%, and one had a variant of uncertain significance. Common challenges included timing of re-contact, age, perceived lack of relevance, inability to travel and limited insurance coverage.
There are several barriers to genetic counseling and testing follow-up after universal tumor testing, and uninformative genetic test results present a management challenge. It is important to consider these limitations when implementing an approach to screening endometrial cancer patients for Lynch syndrome.
确定影响子宫内膜癌患者进行林奇综合征普遍肿瘤检测后遗传咨询接受情况及基因检测结果的因素。
研究人群包括两组未经选择的子宫内膜癌患者队列，一组408例为回顾性确定，另一组206例为前瞻性确定。对这些肿瘤进行错配修复蛋白表达的免疫组织化学检测和/或微卫星不稳定性分析。对MLH1蛋白缺失的肿瘤进行MLH1甲基化分析。如果肿瘤显示MSH2、MSH6或PMS2免疫组织化学缺失、MLH1缺失且无MLH1启动子甲基化和/或微卫星不稳定性，则肿瘤研究被认为提示林奇综合征。联系肿瘤研究提示林奇综合征的参与者并为其提供遗传咨询和检测。
在回顾性队列中，11%的患者肿瘤研究提示林奇综合征，42%的患者接受了遗传咨询。40%检测到种系突变，1例有意义未明的变异。在前瞻性队列中，8.7%的患者肿瘤检测提示林奇综合征；72%的患者接受了遗传咨询。40%发现种系突变，1例有意义未明的变异。常见挑战包括再次联系的时机、年龄、认为缺乏相关性、无法出行和保险覆盖范围有限。
普遍肿瘤检测后遗传咨询和检测随访存在若干障碍，无信息价值的基因检测结果带来管理挑战。在实施子宫内膜癌患者林奇综合征筛查方法时，考虑这些局限性很重要。
