%0 Journal Article
%T Low frequency of defective mismatch repair in a population-based series of upper urothelial carcinoma
%A Kajsa M Ericson
%A Anna P Isinger
%A Bj£¿rn L Isfoss
%A Mef C Nilbert
%J BMC Cancer
%D 2005
%I BioMed Central
%R 10.1186/1471-2407-5-23
%X We 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.A 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.This 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.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]. Hereditary factors also contribute to the development of UUC with a 2-fold increased risk among first-degree relatives [3]. The familial cases develop due to site-specific inheritance as well as within the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome [1,3-5]. 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¨C60%), ovarian cancer (10¨C15%), 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]. Although HNPCC-patients have a 14 to 75-fold increased risk of UUC, with the highest risks reported for carriers of mutations in MSH2, the absolute lifetime risk for mutation carriers to develop UUC is <10% [7-9].HNPCC is caused by a germl
%U http://www.biomedcentral.com/1471-2407/5/23