上尿路尿路上皮癌(UTUC)是与Lynch综合征(LS)相关的第三大常见恶性肿瘤。目前的欧洲泌尿外科指南建议对60岁以下的UTUC患者进行LS筛查。在这项研究中,我们检查了一组UTUC患者与LS的潜在关联,以确定当前指南在检测LS方面的敏感性.在12年期间(2010-2022年),共有180例确诊为UTUC的患者被纳入研究。在15/180名患者(8.3%)中鉴定出DNA错配修复蛋白(MMRp)表达的缺失。最终在8例患者中进行了种系分析,在5例患者中确认了LS(2.8%),MSH6中包括4个种系突变和MSH2中的1个种系突变。与LS相关的UTUC包括3名女性和2名男性,平均年龄为66.2岁(中位数为71岁,范围46-75岁)。5例LS患者中有4例(均为MSH6突变)年龄大于65岁(平均年龄71.3岁,中位数72岁)。我们的发现表明,LS相关的UTUC可以发生在60岁以上的LS患者中。与以前的研究主要使用已经诊断为LS的高度预选人群相比,我们队列中最常见的突变涉及MSH6基因.所有MSH6突变携带者>65岁,UTUC是2/4患者的首次LS表现。根据目前的筛查指南,显著比例的LS相关UTUC患者可能漏诊.我们建议对所有UTUC进行通用免疫组织化学MMRp筛查,无论年龄和临床病史。
Upper tract urothelial carcinoma (UTUC) is the third most common malignancy associated with Lynch syndrome (LS). The current European urology
guidelines recommend screening for LS in patients with UTUC up to the age of 60 years. In this study, we examined a cohort of patients with UTUC for potential association with LS in order to establish the sensitivity of current
guidelines in detecting LS. A total of 180 patients with confirmed diagnosis of UTUC were enrolled in the study during a 12-year period (2010-2022). Loss of DNA-mismatch repair proteins (MMRp) expression was identified in 15/180 patients (8.3%). Germline analysis was eventually performed in 8 patients confirming LS in 5 patients (2.8%), including 4 germline mutations in MSH6 and 1 germline mutation in MSH2. LS-related UTUC included 3 females and 2 males, with a mean age of 66.2 years (median 71 years, range 46-75 years). Four of five LS patients (all with MSH6 mutation) were older than 65 years (mean age 71.3, median 72 years). Our findings indicate that LS-associated UTUCs can occur in patients with LS older than 60 years. In contrast to previous studies which used mainly highly pre-selected populations with already diagnosed LS, the most frequent mutation in our cohort involved MSH6 gene. All MSH6 mutation carriers were > 65 years, and UTUC was the first LS manifestation in 2/4 patients. Using current screening
guidelines, a significant proportion of patients with LS-associated UTUC may be missed. We suggest universal immunohistochemical MMRp screening for all UTUCs, regardless of age and clinical history.