School of Surgery, University of Western Australia, Crawley, WA; Genetic Services of Western Australia, King Edward Memorial Hospital, Subiaco, WA; School of Paediatrics and Child Health, University of Western Australia, Crawley, WA.
Int J Cancer. 2014 Sep 1;135(5):1085-91. doi: 10.1002/ijc.28744. Epub 2014 Feb 24.
We showed earlier that routine screening for microsatellite instability (MSI) and loss of mismatch repair (MMR) protein expression in colorectal cancer (CRC) led to the identification of previously unrecognized cases of Lynch syndrome (LS). We report here the results of screening for LS in Western Australia (WA) during 1994-2012. Immunohistochemistry (IHC) for loss of MMR protein expression was performed in routine pathology laboratories, while MSI was detected in a reference molecular pathology laboratory. Information on germline mutations in MMR genes was obtained from the state's single familial cancer registry. Prior to the introduction of routine laboratory-based screening, an average of 2-3 cases of LS were diagnosed each year amongst WA CRC patients. Following the implementation of IHC and/or MSI screening for all younger (<60 years) CRC patients, this has increased to an average of 8 LS cases diagnosed annually. Based on our experience in WA, we propose three key elements for successful population-based screening of LS. First, for all younger CRC patients, reflex IHC testing should be carried out in accredited pathology services with ongoing quality control. Second, a state- or region-wide reference laboratory for MSI testing should be established to confirm abnormal or suspicious IHC test results and to exclude sporadic cases by carrying out BRAF mutation or MLH1 methylation testing. Finally, a state or regional LS coordinator is essential to ensure that all appropriate cases identified by laboratory testing are referred to and attend a Familial Cancer Clinic for follow-up and germline testing.
我们之前已经证明，在结直肠癌（CRC）中常规筛查微卫星不稳定性（MSI）和错配修复（MMR）蛋白表达缺失可鉴定出先前未被识别的林奇综合征（LS）病例。我们在此报告 1994 年至 2012 年在西澳大利亚（WA）进行 LS 筛查的结果。在常规病理实验室中进行 MMR 蛋白表达缺失的免疫组织化学（IHC）检测，而 MSI 则在参考分子病理学实验室中检测。MMR 基因种系突变的信息来自该州的单一家族癌症登记处。在引入常规实验室为基础的筛查之前，WA CRC 患者中每年平均诊断出 2-3 例 LS 病例。在对所有年轻（<60 岁）CRC 患者实施 IHC 和/或 MSI 筛查后，每年平均诊断出 8 例 LS 病例。基于我们在 WA 的经验，我们提出了成功进行 LS 人群筛查的三个关键要素。首先，对于所有年轻的 CRC 患者，应在经过认证的病理服务机构中进行反射性 IHC 测试，并进行持续的质量控制。其次，应建立一个州或区域范围内的 MSI 测试参考实验室，以确认异常或可疑的 IHC 测试结果，并通过进行 BRAF 突变或 MLH1 甲基化测试排除散发性病例。最后，州或地区的 LS 协调员对于确保通过实验室测试识别的所有合适病例都被转诊并参加家族性癌症诊所进行随访和种系测试至关重要。
