Metcalfe Michael J, Petros Firas G, Rao Priya, Mork Maureen E, Xiao Lianchun, Broaddus Russell R, Matin Surena F
Department of Urology, University of Texas M. D. Anderson Cancer Center, Houston, Texas.
Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, Texas.
J Urol. 2018 Jan;199(1):60-65. doi: 10.1016/j.juro.2017.08.002. Epub 2017 Aug 7.
Patients with Lynch syndrome are at risk for upper tract urothelial carcinoma. We sought to identify the incidence and most reliable means of point of care screening for Lynch syndrome in patients with upper tract urothelial carcinoma.
A total of 115 consecutive patients with upper tract urothelial carcinoma without a history of Lynch syndrome were universally screened during followup from January 2013 through July 2016. We evaluated patient and family history using AMS (Amsterdam criteria) I and II, and tumor immunohistochemistry for mismatch repair proteins and microsatellite instability. Patients who were positive for AMS I/II, microsatellite instability or immunohistochemistry were classified as potentially having Lynch syndrome and referred for clinical genetic analysis and counseling. Patients with known Lynch syndrome served as positive controls.
Of the 115 patients 16 (13.9%) screened positive for potential Lynch syndrome. Of these patients 7.0% met AMS II criteria, 11.3% had loss of at least 1 mismatch repair protein and 6.0% had high microsatellite instability. All 16 patients were referred for germline testing, 9 completed genetic analysis and counseling, and 6 were confirmed to have Lynch syndrome. All 7 patients with upper tract urothelial carcinoma who had a known history of Lynch syndrome were positive for AMS II criteria and at least a single mismatch repair protein loss while 5 of 6 had high microsatellite instability.
We identified 13.9% of upper tract urothelial carcinoma cases as potential Lynch syndrome and 5.2% as confirmed Lynch syndrome at the point of care. These findings have important implications for universal screening of upper tract urothelial carcinoma, representing one of the highest rates of undiagnosed genetic disease in a urological cancer.
林奇综合征患者有发生上尿路尿路上皮癌的风险。我们试图确定上尿路尿路上皮癌患者中林奇综合征即时护理筛查的发生率及最可靠方法。
2013年1月至2016年7月随访期间，对115例无林奇综合征病史的连续性上尿路尿路上皮癌患者进行了全面筛查。我们使用阿姆斯特丹标准（AMS）I和II评估患者及其家族史，并对肿瘤进行错配修复蛋白免疫组化和微卫星不稳定性检测。AMS I/II、微卫星不稳定性或免疫组化呈阳性的患者被分类为可能患有林奇综合征，并被转诊进行临床基因分析和咨询。已知林奇综合征的患者作为阳性对照。
115例患者中，16例（13.9%）筛查出可能患有林奇综合征。其中，7.0%符合AMS II标准，11.3%至少有1种错配修复蛋白缺失，6.0%有高微卫星不稳定性。所有16例患者均被转诊进行种系检测，9例完成了基因分析和咨询，6例被确诊为林奇综合征。所有7例有林奇综合征已知病史的上尿路尿路上皮癌患者AMS II标准呈阳性，且至少有1种错配修复蛋白缺失，而6例中有5例有高微卫星不稳定性。
我们在即时护理中确定13.9%的上尿路尿路上皮癌病例为可能的林奇综合征，5.2%为确诊的林奇综合征。这些发现对上尿路尿路上皮癌的全面筛查具有重要意义，代表了泌尿生殖系统癌症中未诊断出的遗传疾病的最高发生率之一。
