Hartmann, Arndt and Zanardo, Livia and Bocker-Edmonston, Tina and Blaszyk, Hagen and Dietmaier, Wolfgang and Stoehr, Robert and Cheville, John C. and Junker, Kerstin and Wieland, Wolf and Knuechel, Ruth and Rueschoff, Josef and Hofstaedter, Ferdinand and Fishel, Richard (2002) Frequent microsatellite instability in sporadic tumors of the upper urinary tract. Cancer research 62 (23), pp. 6796-6802.
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Urothelial carcinoma of the renal pelvis and ureter may develop sporadically or as a manifestation of hereditary nonpolyposis colorectal cancer. The majority of hereditary nonpolyposis colorectal cancer is caused by mutation of the human DNA mismatch repair (MMR) genes and is detected by associated microsatellite instability (MSI). Seventy-three unselected urothelial carcinomas of the ureter and/or renal pelvis were screened for MSI using the National Cancer Institute-designated reference panel (plus BAT40). Instability of at least two microsatellite markers (MSI-high) was detected in 15 samples (21%). Immunohistochemical staining of the MMR proteins (hMSH2, hMLH1, or hMSH6) was absent in 13 of 15 (87%) MSI tumors, and alteration of coding sequence microsatellites (TGFbetaRII, Bax, hMSH3, and hMSH6) was found at frequencies of 7-33% in these samples. Tumors with MSI had significantly different clinical and histopathological features including higher prevalence in female patients, low tumor stage and grade, and a papillary and frequently inverted growth pattern. Our results suggest a molecular pathway of tumorigenesis that is similar to MMR-deficient colorectal cancers and consistent with the notion that the site distributions of hereditary or sporadic MSI-high tumors may reflect tissue-specific susceptibility to lesions processed by the MMR machinery.
|Institutions:||Medicine > Lehrstuhl für Pathologie|
|Subjects:||600 Technology > 610 Medical sciences Medicine|
|Created at the University of Regensburg:||Unknown|
|Deposited On:||18 Jun 2010 08:42|
|Last Modified:||18 Jun 2010 08:42|