Patrick Joost1, Christina Therkildsen2, Mev Dominguez-Valentin3, Mats Jönsson3, Mef Nilbert2. 1. Department of Oncology and Pathology, Institute of Clinical Sciences, Lund University, Lund, Sweden. Electronic address: patrick.joost@med.lu.se. 2. Department of Oncology and Pathology, Institute of Clinical Sciences, Lund University, Lund, Sweden; HNPCC-Register, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark. 3. Department of Oncology and Pathology, Institute of Clinical Sciences, Lund University, Lund, Sweden.
Abstract
OBJECTIVE: To evaluate the risk of urothelial cancer in the upper urinary tract and the bladder, determine the contribution from the different mismatch-repair genes, and define clinical characteristics of urothelial cancer in Lynch syndrome. MATERIALS AND METHODS: The national hereditary nonpolyposis colorectal cancer registry was used to identify all 288 Lynch syndrome families in Denmark. Urothelial cancers that developed in mutation carriers and in their first-degree relatives were identified, mismatch-repair status was assessed, clinicopathologic variables were defined, and cumulative lifetime risks were determined. RESULTS: In total, 48 cancers of the ureter, 34 cancers of the renal pelvis, and 54 urinary bladder cancers developed at a mean age of 61 (24-89) years. The tumors were typically of high grade, showed loss of mismatch-repair protein expression in 90% of the tumors and microsatellite instability in 23% of the tumors. Mutations in MSH2 were overrepresented (73%), and MSH2 mutation carriers were at a significantly increased risk of developing urinary tract cancer compared with individuals with mutations in MLH1 or MSH6. CONCLUSION: Cancers of the upper urinary tract and the urinary bladder are included in the Lynch syndrome tumor spectrum. Urothelial cancers are predominantly linked to MSH2 mutations, which suggest that surveillance should be targeted at individuals with mutations herein.
OBJECTIVE: To evaluate the risk of urothelial cancer in the upper urinary tract and the bladder, determine the contribution from the different mismatch-repair genes, and define clinical characteristics of urothelial cancer in Lynch syndrome. MATERIALS AND METHODS: The national hereditary nonpolyposis colorectal cancer registry was used to identify all 288 Lynch syndrome families in Denmark. Urothelial cancers that developed in mutation carriers and in their first-degree relatives were identified, mismatch-repair status was assessed, clinicopathologic variables were defined, and cumulative lifetime risks were determined. RESULTS: In total, 48 cancers of the ureter, 34 cancers of the renal pelvis, and 54 urinary bladder cancers developed at a mean age of 61 (24-89) years. The tumors were typically of high grade, showed loss of mismatch-repair protein expression in 90% of the tumors and microsatellite instability in 23% of the tumors. Mutations in MSH2 were overrepresented (73%), and MSH2 mutation carriers were at a significantly increased risk of developing urinary tract cancer compared with individuals with mutations in MLH1 or MSH6. CONCLUSION: Cancers of the upper urinary tract and the urinary bladder are included in the Lynch syndrome tumor spectrum. Urothelial cancers are predominantly linked to MSH2 mutations, which suggest that surveillance should be targeted at individuals with mutations herein.
Authors: Jonathan W Wischhusen; Chinedu Ukaegbu; Tara G Dhingra; Hajime Uno; Fay Kastrinos; Sapna Syngal; Matthew B Yurgelun Journal: Cancer Epidemiol Biomarkers Prev Date: 2019-10-15 Impact factor: 4.254
Authors: Maria I Carlo; Vignesh Ravichandran; Preethi Srinavasan; Chaitanya Bandlamudi; Yelena Kemel; Ozge Ceyhan-Birsoy; Semanti Mukherjee; Diana Mandelker; Joshua Chaim; Andrea Knezevic; Satshil Rana; Zarina Fnu; Kelsey Breen; Angela G Arnold; Aliya Khurram; Kaitlyn Tkachuk; Catharine K Cipolla; Ashley Regazzi; A Ari Hakimi; Hikmat Al-Ahmadie; Guido Dalbagni; Karen A Cadoo; Michael F Walsh; Min-Yuen Teo; Samuel A Funt; Jonathan A Coleman; Bernard H Bochner; Gopa Iyer; David B Solit; Zsofia K Stadler; Liying Zhang; Jonathan E Rosenberg; Barry S Taylor; Mark E Robson; Michael F Berger; Joseph Vijai; Dean F Bajorin; Kenneth Offit Journal: J Clin Oncol Date: 2019-12-03 Impact factor: 44.544
Authors: Christina Therkildsen; Steen Ladelund; Lars Smith-Hansen; Lars Joachim Lindberg; Mef Nilbert Journal: Br J Cancer Date: 2017-10-24 Impact factor: 7.640