Department of Gynaecologic Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, the Netherlands.
Department of Clinical Genetics, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, the Netherlands.
Gynecol Oncol. 2021 Mar;160(3):771-776. doi: 10.1016/j.ygyno.2020.12.028. Epub 2021 Jan 6.
In the Netherlands a nationwide guideline was introduced in 2016, which recommended routine Lynch syndrome screening (LSS) for all women with endometrial cancer (EC) <70 years of age. LSS consists of immunohistochemical (IHC) staining for loss of mismatch repair (MMR) protein expression, supplemented with MLH1 methylation analysis if indicated. Test results are evaluated by the treating gynaecologist, who refers eligible patients to a clinical geneticist. We evaluated the implementation of this guideline.
From the nation-wide pathology database we selected all women diagnosed with EC < 70 years of age, treated from 1.6.2016-1.6.2017 in 14 hospitals. We collected data on the results of LSS and follow up of cases with suspected LS.
In 183 out of 204 tumours (90%) LSS was performed. In 41 cases (22%) MMR protein expression was lost, in 25 cases due to hypermethylation of the MLH1 promotor. One patient was known with a pathogenic MLH1 variant. The option of genetic counselling was discussed with 12 of the 15 remaining patients, of whom three declined. After counselling by the genetic counsellor nine patients underwent germline testing. In two no pathogenic germline variant was detected, two were diagnosed with a pathogenic PMS2 variant, and five with a pathogenic MSH6 variant, in concordance with the IHC profiles.
Coverage of LSS was high (90%), though referral for genetic counselling could be improved. Gynaecologists ought to be aware of the benefits and possible drawbacks of knowing mutational status, and require training in discussing this with their patients.
荷兰于 2016 年推出了一项全国性指南，建议对所有<70 岁的子宫内膜癌（EC）女性进行常规林奇综合征筛查（LSS）。LSS 包括免疫组织化学（IHC）染色以检测错配修复（MMR）蛋白表达缺失，如果有必要，还可以进行 MLH1 甲基化分析。检测结果由治疗妇科医生进行评估，然后将符合条件的患者转介给临床遗传学家。我们评估了该指南的实施情况。
我们从全国性的病理数据库中选择了所有<70 岁且在 2016 年 6 月 1 日至 2017 年 6 月 1 日期间在 14 家医院治疗的 EC 女性。我们收集了 LSS 结果和疑似 LS 病例的随访数据。
在 204 例肿瘤中有 183 例（90%）进行了 LSS。在 41 例（22%）中，MMR 蛋白表达缺失，其中 25 例是由于 MLH1 启动子的甲基化。1 例患者存在致病性 MLH1 变异。对 15 例剩余患者中的 12 例讨论了遗传咨询的选择，其中 3 例拒绝。在遗传咨询师咨询后，9 例患者接受了种系检测。在 2 例中未检测到致病性种系变异，2 例被诊断为致病性 PMS2 变异，5 例为致病性 MSH6 变异，与 IHC 图谱一致。
LSS 的覆盖率很高（90%），但遗传咨询的转诊可以进一步提高。妇科医生应该意识到了解突变状态的益处和可能的缺点，并需要接受与患者讨论这一问题的培训。
