Irons Robin F, Contino Krysta M, Horte Janice J, Levin Brooke, Mattie Kristin D, Wight Margaret, Kwiatt Michael E, Behling Kathryn C, Edmonston Tina B, McClane Steven J
Department of Surgery, Cooper University Hospital, Office of Surgical Education, 3 Cooper Plaza, Suite 411, Camden, NJ, 08103, USA.
Department of Medicine, Cooper University Hospital, 401 Haddon Avenue, E&R Building, Third Floor, Camden, NJ, 08103, USA.
Int J Colorectal Dis. 2017 Sep;32(9):1345-1348. doi: 10.1007/s00384-017-2849-x. Epub 2017 Jun 29.
Lynch syndrome (LS) is a hereditary condition that increases one's risk of developing colorectal, endometrial, and other extracolonic cancers. MD Anderson Cancer Center at Cooper implemented a reflex screening protocol for DNA mismatch repair (dMMR) deficiency. Those with findings suspicious for LS were referred for genetic counseling (GC). Our goal was to assess compliance with GC and factors associated with successful follow-up.
Immunohistochemistry (IHC) for the MMR proteins MSH2, MLH1, MSH6, and PMS2 was performed on all colorectal tumor resections from patients ≤70 years old and all stage II cancers. Tumors with loss of MLH1/PMS2 were subsequently tested for BRAF mutation or MLH1 promoter methylation to identify tumors with likely epigenetic inactivation of MLH1. Patients with loss of MLH1/PMS2 without BRAF mutations or with absence of MLH1 promoter methylation and those with loss of MSH2/MSH6 were referred to GC. Compliance with GC was assessed.
Between March 2014 and August 2016, 203 tumors were tested by IHC. Fifteen (7.4%) patients had abnormal MMR protein expression patterns in the absence of BRAF mutation or MLH1 promoter methylation suggestive of possible LS. GC compliance was 35.7% overall and 85.7% in those with family history of LS-associated cancers.
Overall, GC compliance was relatively low in our study. Interestingly, patients with a strong family history of LS-associated neoplasms were more likely to pursue GC. In the future, assessing and addressing barriers to seeking GC will provide opportunities to improve patient care through increased identification of patients with cancer predisposition syndromes.
林奇综合征（LS）是一种遗传性疾病，会增加患结直肠癌、子宫内膜癌和其他结肠外癌症的风险。库珀市的MD安德森癌症中心实施了一项针对DNA错配修复（dMMR）缺陷的反射性筛查方案。那些发现有疑似LS症状的患者会被转介进行遗传咨询（GC）。我们的目标是评估GC的依从性以及与成功随访相关的因素。
对所有年龄≤70岁患者的结直肠肿瘤切除术标本以及所有II期癌症进行MMR蛋白MSH2、MLH1、MSH6和PMS2的免疫组织化学（IHC）检测。对于MLH1/PMS2缺失的肿瘤，随后检测BRAF突变或MLH1启动子甲基化，以识别可能存在MLH1表观遗传失活的肿瘤。MLH1/PMS2缺失且无BRAF突变或MLH1启动子甲基化的患者以及MSH2/MSH6缺失的患者被转介进行GC。评估GC的依从性。
在2014年3月至2016年8月期间，通过IHC检测了203个肿瘤。15名（7.4%）患者在无BRAF突变或MLH1启动子甲基化的情况下出现异常的MMR蛋白表达模式，提示可能为LS。总体GC依从率为35.7%，有LS相关癌症家族史的患者中GC依从率为85.7%。
总体而言，在我们的研究中GC依从率相对较低。有趣的是，有LS相关肿瘤家族史的患者更有可能接受GC。未来，评估并解决寻求GC的障碍将为通过增加对癌症易感性综合征患者的识别来改善患者护理提供机会。
