Lynch Syndrome: Its Impact on Urothelial Carcinoma

• Main Authors: Andrea Katharina Lindner, Gert Schachtner, Gennadi Tulchiner, Martin Thurnher, Gerold Untergasser, Peter Obrist, Iris Pipp, Fabian Steinkohl, Wolfgang Horninger, Zoran Culig, Renate Pichler
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: International Journal of Molecular Sciences
• Subjects: Lynch syndrome; urothelial cancer; upper urinary tract; DNA mismatch repair genes; MMR; microsatellite instability
• Online Access: https://www.mdpi.com/1422-0067/22/2/531
• ISSN: 1661-6596; 1422-0067

Lynch syndrome, known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal-dominant familial cancer syndrome with an increased risk for urothelial cancer (UC). Mismatch repair (MMR) deficiency, due to pathogenic variants in <i>MLH1</i>, <i>MSH2</i>, <i>MSH6</i>, and <i>PMS2</i>, and microsatellite instability, are known for development of Lynch syndrome (LS) associated carcinogenesis. UC is the third most common cancer type in LS-associated tumors. The diversity of germline variants in the affected MMR genes and their following subsequent function loss might be responsible for the variation in cancer risk, suggesting an increased risk of developing UC in <i>MSH2</i> mutation carriers. In this review, we will focus on LS-associated UC of the upper urinary tract (UUT) and bladder, their germline profiles, and outcomes compared to sporadic UC, the impact of genetic testing, as well as urological follow-up strategies in LS. In addition, we present a case of metastatic LS-associated UC of the UUT and bladder, achieving complete response during checkpoint inhibition since more than 2 years.