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Urinary Tract Cancer in Lynch Syndrome; Increased Risk in Carriers of MSH2 Mutations

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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.

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, clinico-pathologic variables were defined and cumulative life-time 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 significantly increased risk of urinary tract cancer compared individuals with mutations in MLH1/MSH6.

CONCLUSIONS: Cancers of the upper urinary tract as well as 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.

OriginalsprogEngelsk
TidsskriftUrology
Vol/bind86
Udgave nummer6
Sider (fra-til)1212-1217
ISSN0090-4295
DOI
StatusUdgivet - dec. 2015

ID: 45642392