167 BIOLOGICAL CHARACTERISTICS IN BLADDER CANCER DEPEND ON THE TYPE OF GENETIC INSTABILITY - CLOSE ASSOCIATION OF CENTROSOME AMPLIFICATION WITH DISEASE PROGRESSION

Abstract

You have accessJournal of UrologyUrothelial Cancer: Natural History & Pathophysiology/Markers1 Apr 2010167 BIOLOGICAL CHARACTERISTICS IN BLADDER CANCER DEPEND ON THE TYPE OF GENETIC INSTABILITY - CLOSE ASSOCIATION OF CENTROSOME AMPLIFICATION WITH DISEASE PROGRESSION Yoshiaki Yamamoto, Taku Misumi, Kohsuke Sasaki, and Hideyasu Matsuyama Yoshiaki YamamotoYoshiaki Yamamoto More articles by this author , Taku MisumiTaku Misumi More articles by this author , Kohsuke SasakiKohsuke Sasaki More articles by this author , and Hideyasu MatsuyamaHideyasu Matsuyama More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.221AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Malignant tumors show an inherent genetic instability that can be classified as microsatellite instability (MSI) or chromosomal instability (CIN). To elucidate the differences in biological characteristics of bladder cancer between the two types of genetic instability, the expression of the mismatch repair (MMR) proteins, Aurora-A, p53, PLK1 and BUBR1 proteins, the number of centrosomes, numerical aberrations of chromosomes and 20q13, and DNA ploidy were examined in 100 human urothelial carcinomas of the bladder. METHODS Expressions of the MLH1, MSH2, Aurora-A, p53, PLK1 and BUBR1 proteins, and the numbers of centrosomes were immunohistochemically assessed. Numerical aberrations of chromosomes 7, 9, 17 and 20q13 spots were evaluated by fluorescence in situ hybridization (FISH), and DNA ploidy was assessed by laser scanning cytometry. RESULTS The expression levels of the MMR related-proteins decreased in 9 out of 100 tumors. Tumors with low MLH1 or MSH2 expression (designated as MSI cancers) were not linked with centrosome amplification, Aurora-A, PLK1, and BUBR1 overexpression, increased p53 immunoreactivity, 20q13 gain, DNA aneuploidy, and disease progression. MSI cancers showed a favorable prognosis. CIN cancers (49 cases), defined as tumors with a large intercellular variation in centromere copy numbers, were associated more frequently with centrosome amplification, Aurora-A, PLK1, and BUBR1 overexpression, increased p53 immunoreactivity and 20q13 gain than the others (51 cases). Tumors with disease progression were included in the CIN cancer group. Of the CIN-related molecular markers investigated in this study, centrosome amplification was the strongest predictor for disease progression. CONCLUSIONS The present observations suggest that there are differences in the biological characteristics of the two types of genetic instability, and that CIN may be dominant pathway relevant for malignant phenotype in bladder cancer. Ube, Japan© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e67-e68 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yoshiaki Yamamoto More articles by this author Taku Misumi More articles by this author Kohsuke Sasaki More articles by this author Hideyasu Matsuyama More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...