Prognostic Implications of p53 Gene Mutations in Bladder Tumors

Abstract

No AccessJournal of UrologyCLINICAL UROLOGY: Original Articles1 Feb 2003Prognostic Implications of p53 Gene Mutations in Bladder Tumors J.G. LORENZO-ROMERO, A.S. SALINAS-SÁNCHEZ, J.M. GIMÉNEZ-BACHS, F. SÁNCHEZ-SÁNCHEZ, J. ESCRIBANO-MARTÍNEZ, M. SEGURA-MARTÍN, I.R. HERNÁNDEZ-MILLÁN, and J.A. VIRSEDA-RODRÍGUEZ J.G. LORENZO-ROMEROJ.G. LORENZO-ROMERO More articles by this author , A.S. SALINAS-SÁNCHEZA.S. SALINAS-SÁNCHEZ More articles by this author , J.M. GIMÉNEZ-BACHSJ.M. GIMÉNEZ-BACHS More articles by this author , F. SÁNCHEZ-SÁNCHEZF. SÁNCHEZ-SÁNCHEZ More articles by this author , J. ESCRIBANO-MARTÍNEZJ. ESCRIBANO-MARTÍNEZ More articles by this author , M. SEGURA-MARTÍNM. SEGURA-MARTÍN More articles by this author , I.R. HERNÁNDEZ-MILLÁNI.R. HERNÁNDEZ-MILLÁN More articles by this author , and J.A. VIRSEDA-RODRÍGUEZJ.A. VIRSEDA-RODRÍGUEZ More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)63941-9AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Alterations in the p53 gene related to neoplastic progression were studied in tumor tissue samples from patients with transitional cell carcinoma and correlated with classic staging parameters. On this basis, biological characterization of the tumor was performed to establish subgroups of patients at high risk and those with a more favorable prognosis. Materials and Methods: This observational, analytical and cross-sectional study included 115 patients divided into 4 homogeneous groups of 1—control, 2—primary superficial transitional cell carcinoma, 3—recurrent superficial transitional cell carcinoma, and 4—infiltrative transitional cell carcinoma. DNA was obtained from tumor tissue samples and polymerase chain reaction-single strand conformational polymorphism analysis was performed on exons 5 to 9 of the p53 gene. Samples showing mutations were submitted to automatic sequencing. Statistics included bivariate analysis and logistic regression. Results: Of the tumors the 63.8% were superficial and 37.2% were infiltrative transitional cell carcinoma. Of the infiltrative tumors 23.5% (8 of 34) resulted from recurrent transitional cell carcinoma. Mutations were found in samples from 46.8% of patients, all with bladder tumors. There was a trend toward increasing appearance of mutations as the size of the tumor, number of tumor implants, degree of dedifferentiation and stage of local infiltration increased. The presence of mutations in p53 was 2.5 times greater in infiltrative tumors than in low stage and 4.3 times greater in moderate to high grade than in low grade tumors. All mutations found were point mutations and 79.25% provoked severe alterations in protein structure. Conclusions: Mutations in the p53 gene are mainly point mutations that aggregate in hot spots, and provoke genetic instability and substantial changes that alter p53 function, implying a trend to tumor progression and dissemination (with a greater proportion of mutations in high stage high grade tumors). Since a large percentage of bladder tumors are under staged, analysis of p53 gene mutations could be useful as a factor for prognosis and therapeutic decisions. References 1 : The genetics of transitional cell carcinoma: progress and potential clinical application. BJU Int1999; 84: 412. Google Scholar 2 : Mutations of cell cycle regulators. Biological and clinical implications for human neoplasia. Am J Pathol1995; 147: 545. Google Scholar 3 : Genetic alterations in bladder cancer. Lancet1993; 342: 469. Google Scholar 4 : Cancer genetics. Is p53 the only real tumor suppressor gene?. 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Oncogene1991; 6: 1691. Google Scholar 27 : Genetic and molecular markers of urothelial premalignancy and malignancy. Scand J Urol Nephrol2000; 205: 82. Google Scholar 28 : Progressive increases in de novo methylation of CpG islands in bladder cancer. Cancer Res2000; 60: 2473. Google Scholar From the Urology Service, Hospital and University Complex of Albacete and the Department of Genetics, Faculty of Medicine, University of Castilla-La Mancha, Albacete, Spain© 2003 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 169Issue 2February 2003Page: 492-499 Advertisement Copyright & Permissions© 2003 by American Urological Association, Inc.Keywordspolymerase chain reactionpolymorphism, single-stranded conformationalcarcinoma, transitional cellgenes, p53prognosisMetricsAuthor Information J.G. LORENZO-ROMERO More articles by this author A.S. SALINAS-SÁNCHEZ More articles by this author J.M. GIMÉNEZ-BACHS More articles by this author F. SÁNCHEZ-SÁNCHEZ More articles by this author J. ESCRIBANO-MARTÍNEZ More articles by this author M. SEGURA-MARTÍN More articles by this author I.R. HERNÁNDEZ-MILLÁN More articles by this author J.A. VIRSEDA-RODRÍGUEZ More articles by this author Expand All Advertisement PDF downloadLoading ...