Abstract
BackgroundUpper urothelial cancer (UUC), i.e. transitional cell carcinomas of the renal pelvis and the ureter, occur at an increased frequency in patients with hereditary nonpolyposis colorectal cancer (HNPCC). Defective mismatch repair (MMR) specifically characterizes HNPCC-associated tumors, but also occurs in subsets of some sporadic tumors, e.g. in gastrointestinal cancer and endometrial cancer.MethodsWe assessed the contribution of defective MMR to the development of UUC in a population-based series from the southern Swedish Cancer Registry, through microsatellite instability (MSI) analysis and immunohistochemical evaluation of expression of the MMR proteins MLH1, PMS2, MSH2, and MSH6.ResultsA MSI-high phenotype was identified in 9/216 (4%) successfully analyzed patients and a MSI-low phenotype in 5/216 (2%). Loss of MMR protein immunostaining was found in 11/216 (5%) tumors, and affected most commonly MSH2 and MSH6.ConclusionThis population-based series indicates that somatic MMR inactivation is a minor pathway in the development of UUC, but tumors that display defective MMR are, based on the immunohistochemical expression pattern, likely to be associated with HNPCC.
Highlights
Upper urothelial cancer (UUC), i.e. transitional cell carcinomas of the renal pelvis and the ureter, occur at an increased frequency in patients with hereditary nonpolyposis colorectal cancer (HNPCC)
Individuals with HNPCC are at increased risk for several types of cancer, with the highest life-time risks for colorectal cancer (80%), endometrial cancer (40–60%), ovarian cancer (10–15%), cancer of the small intestine and upper urothelial cancer [4], and the revised Amsterdam criteria for the diagnosis of HNPCC consider these tumor types to be associated with the syndrome [6]
Immunohistochemistry Immunohistochemical staining for the MMR proteins gave evaluable results for MLH1 in 211 tumors, MSH2 in 216, MSH6 in 200 tumors and PMS2 in 215 tumors
Summary
Upper urothelial cancer (UUC), i.e. transitional cell carcinomas of the renal pelvis and the ureter, occur at an increased frequency in patients with hereditary nonpolyposis colorectal cancer (HNPCC). Upper urothelial carcinomas (UUC) represent about 5% of the urinary tract tumors, with transitional cell carcinomas of the renal pelvis and the ureter being the most common [1]. Exogenous agents such as smoking and occupational exposures to e.g. acrylamines constitute risk factors that are estimated to cause up to half of the tumors [2]. HNPCCpatients have a 14 to 75-fold increased risk of UUC, with the highest risks reported for carriers of mutations in (page number not for citation purposes)
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