Lim Amy, Rao Priya, Matin Surena F
Department of Urology.
Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Curr Opin Urol. 2019 Jul;29(4):357-363. doi: 10.1097/MOU.0000000000000639.
An overview of urologic malignancies in Lynch syndrome and the current state of research.
Upper tract urothelial carcinoma (UTUC) is the third most common malignancy in Lynch syndrome. Establishment and utilization of a sensitive and practical screening method for Lynch syndrome in patients presenting with UTUC is overdue. Next-generation sequencing to evaluate for microsatellite instability (MSI) and detect mutations of mismatch repair (MMR) genes may be the future of Lynch syndrome screening. Epidemiologic data and molecular characterization suggest bladder urothelial carcinoma (BUC) and prostate cancer (PCA) as unrecognized components of Lynch syndrome. Small studies suggest that Lynch syndrome may predispose individuals to adrenocortical carcinoma. Testicular cancer literature focuses on characterizing MSI and MMR gene expression as it relates to chemotherapy sensitivity; outcomes suggest a potential avenue to investigate its relationship to Lynch syndrome.
Patients with Lynch syndrome have an increased risk of urologic malignancies, including UTUC and likely BUC and PCA. BUC and PCA have a lower penetrance than UTUC for unknown reasons. Established Lynch syndrome-associated genitourinary tumors will necessitate the development of methods to diagnose Lynch syndrome in patients presenting with these malignancies, in addition to establishing screening guidelines for patients with Lynch syndrome-associated genitourinary tumors.
概述林奇综合征中的泌尿系统恶性肿瘤及当前研究现状。
上尿路尿路上皮癌（UTUC）是林奇综合征中第三常见的恶性肿瘤。对于患有UTUC的患者，建立并应用一种敏感且实用的林奇综合征筛查方法已刻不容缓。通过新一代测序评估微卫星不稳定性（MSI）并检测错配修复（MMR）基因的突变可能是未来林奇综合征筛查的方向。流行病学数据和分子特征表明，膀胱尿路上皮癌（BUC）和前列腺癌（PCA）是林奇综合征中未被认识的组成部分。小型研究表明，林奇综合征可能使个体易患肾上腺皮质癌。睾丸癌相关文献主要关注MSI和MMR基因表达与化疗敏感性的关系；研究结果提示了一条研究其与林奇综合征关系的潜在途径。
林奇综合征患者患泌尿系统恶性肿瘤的风险增加，包括UTUC，可能还有BUC和PCA。由于不明原因，BUC和PCA的外显率低于UTUC。除了为林奇综合征相关泌尿生殖系统肿瘤患者制定筛查指南外，已确定的林奇综合征相关泌尿生殖系统肿瘤还需要开发针对患有这些恶性肿瘤患者的林奇综合征诊断方法。
