CORRELATION BETWEEN p53 OVER EXPRESSION AND RESPONSE TO BACILLUS CALMETTE-GUERIN THERAPY IN A HIGH RISK SELECT POPULATION OF PATIENTS WITH T1G3 BLADDER CANCER

Abstract

No AccessJournal of UrologyClinical Urology: Original Articles1 Mar 1998CORRELATION BETWEEN p53 OVER EXPRESSION AND RESPONSE TO BACILLUS CALMETTE-GUERIN THERAPY IN A HIGH RISK SELECT POPULATION OF PATIENTS WITH T1G3 BLADDER CANCER THIERRY LEBRET, VERONIQUE BECETTE, MICHEL BARBAGELATTA, JEAN-MARIE HERVE, FRANCOIS GAUDEZ, PHILIPPE BARRE, PIERRE-MARIE LUGAGNE, and HENRY BOTTO THIERRY LEBRETTHIERRY LEBRET More articles by this author , VERONIQUE BECETTEVERONIQUE BECETTE More articles by this author , MICHEL BARBAGELATTAMICHEL BARBAGELATTA More articles by this author , JEAN-MARIE HERVEJEAN-MARIE HERVE More articles by this author , FRANCOIS GAUDEZFRANCOIS GAUDEZ More articles by this author , PHILIPPE BARREPHILIPPE BARRE More articles by this author , PIERRE-MARIE LUGAGNEPIERRE-MARIE LUGAGNE More articles by this author , and HENRY BOTTOHENRY BOTTO More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)63731-5AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The aim of this study was to determine if p53 status, assessed before intravesical bacillus Calmette-Guerin (BCG) therapy, can predict clinical outcome in a high risk population of patients with stage T1, grade G3 bladder cancer and if it can be used to select patients responsive to therapy. Material and Methods: After complete transurethral resection 35 patients with T1G3 bladder carcinoma received 6 weekly instillations of BCG and nonresponsive patients received a second course. After treatment cystoscopy and randomized biopsies of the bladder mucosa were performed. Pathologists had sufficient material to perform immunomarking in 25 cases using the peroxidase-antiperoxidase technique with antiprotein monoclonal antibody p53. The results were expressed in percentage of marked nuclei. We established 5% increment thresholds from 0 to 60%. Contingent tables were established, and chi-square and Fisher's exact test were performed for each 5% threshold. Results: Median followup was 51.3 months (range 25 to 114). Of the 25 patients 8 (32%) did not respond to BCG therapy and 17 (68%) did. Immunomarkings were not statistically different between BCG responsive and nonresponsive patients for 0, 5, 10, 20, 35, 40, 45, 55 and 65 thresholds. Chi-square and Fisher's exact test were 0.91 and 0.83, 0.40 and 0.20, 0.58 and 0.29, 0.96 and 0.81, 0.80 and 0.88, 0.67 and 0.73, 0.91 and 0.83, 0.80 and 0.38, 0.69 and 0.32, respectively. Conclusions: Our results indicate that the percentage of p53 immunomarked cell cannot currently be used to predict clinical response to BCG therapy and, therefore, p53 over expression is not a viable indicator of T1G3 recurrence when using this treatment. References 1 : Recurrence, progression and survival in bladder cancer. Scand. J. Urol. Nephrol.1987; 21: 185. Google Scholar 2 : The T1 bladder tumor. Sem. Urol.1990; 8: 254. Google Scholar 3 : Result of 6 weekly intravesical bacillus Calmette-Guerin instillations on the treatment of superficial bladder tumors. J. Urol.1988; 139: 935. Abstract, Google Scholar 4 : Bacillus Calmette-Guerin therapy for superficial bladder cancer: a 10-year followup. J. Urol.1992; 147: 1020. Link, Google Scholar 5 : Genetic alterations during colorectal tumor development. New. Engl. J. Med.1988; 319: 525. Google Scholar 6 : Molecular genetics and biochemical mechanisms in bladder cancer. Oncogenes, tumor suppressor genes and growth factors. Urol. Clin. N. Amer.1992; 19: 629. Google Scholar 7 : Identification of p53 gene mutations in bladder cancers and urine samples. Science1991; 252: 706. Google Scholar 8 : Overexpression of p53 protein in high-risk population of patients with superficial bladder cancer before and after bacillus Calmette-Guerin therapy: correlation to clinical outcome. J. Clin. Oncol.1996; 14: 2646. Google Scholar 9 : p53 immunohistochemistry as an independent prognostic factor for superficial transitional cell carcinoma of the bladder. Brit. J. Cancer1995; 71: 201. Google Scholar 10 : p53 mutation in bladder cancer: correlation between immunohistochemistry (IHC), single strand conformation polymorphism (SSCP) and sequencing. J. Urol.1993; 149: 238A. part 2, abstract 98. Google Scholar 11 : p53 overexpression in formalin fixed, paraffin embedded tissue detected by immunohistochemistry. J. Histochem. Cytochem.1991; 40: 1047. Google Scholar 12 : The p53 protooncogene can act as a suppressor of transformation. Cell1989; 57: 1083. Google Scholar 13 : Nonrandom chromosomal changes in transitional cell carcinoma of the bladder. Cancer Res.1984; 44: 1257. Google Scholar 14 : p53 mutations and prognosis in bladder tumors. J. Urol.1995; 153: 1097. Link, Google Scholar 15 : Allelic loss of chromosome 17p distinguishes high grade from low grade transitional cell carcinomas of the bladder. Cancer Res.1990; 50: 7081. Google Scholar 16 : Association of p53 nuclear overexpression and tumor progression in carcinoma in situ of the bladder. J. Urol.1994; 152: 388. Link, Google Scholar 17 : p53 immunohistochemistry as an independent prognostic factor for superficial transitional cell carcinoma of the bladder. Brit. J. Cancer1995; 71: 201. Google Scholar 18 : Allelic loss of chromosome 17P in urothelial cancer: strong association with invasive phenotype. J. Urol.1992; 148: 1595. Link, Google Scholar 19 : Nuclear overexpression of p53 protein in transitional cell bladder carcinoma: a marker for disease progression. J. Natl. Cancer Inst.1993; 85: 53. Google Scholar 20 : Long-term efficacy of intravesical bacillus Calmette-Guerin for carcinoma in situ: relationship of progression to histological response and p53 nuclear accumulation. J. Urol.1997; 157: 1655. Link, Google Scholar 21 : p53 gene mutation in recurrent superficial bladder cancer. J. Urol.1995; 153: 1711. Link, Google Scholar 22 : Prognostic factors in non-infiltrating carcinoma of the bladder: a preliminary report. Brit. J. Urol.1982; 54: 711. Google Scholar From the Departments of Urology and Pathology, Foch Hospital, Suresnes and Rene Huguenin Center, St. Cloud, France.© 1998 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byLEBRET T, WILLIAM R, WATSON G and FITZPATRICK J (2018) Heat Shock Proteins: Their Role in Urological TumorsJournal of Urology, VOL. 169, NO. 1, (338-346), Online publication date: 1-Jan-2003.Soloway M, Sofer M and Vaidya A (2018) Contemporary Management Of Stage T1 Transitional Cell Carcinoma Of The BladderJournal of Urology, VOL. 167, NO. 4, (1573-1583), Online publication date: 1-Apr-2002. (2018) EDITORIAL COMMENTJournal of Urology, VOL. 165, NO. 1, (46-46), Online publication date: 1-Jan-2001.KONDYLIS F, DEMIRCI S, LADAGA L, KOLM P and SCHELLHAMMER P (2018) OUTCOMES AFTER INTRAVESICAL BACILLUS CALMETTE-GUERIN ARE NOT AFFECTED BY SUBSTAGING OF HIGH GRADE T1 TRANSITIONAL CELL CARCINOMAJournal of Urology, VOL. 163, NO. 4, (1120-1123), Online publication date: 1-Apr-2000.LEBRET T, BOHIN D, KASSARDJIAN Z, HERVE J, MOLINIE V, BARRE P, LUGAGNE P and BOTTO H (2018) RECURRENCE, PROGRESSION AND SUCCESS IN STAGE TA GRADE 3 BLADDER TUMORS TREATED WITH LOW DOSE BACILLUS CALMETTE-GUERIN INSTILLATIONSJournal of Urology, VOL. 163, NO. 1, (63-67), Online publication date: 1-Jan-2000.ZLOTTA A, NOEL J, FAYT I, DROWART A, VAN VOOREN J, HUYGEN K, SIMON J and SCHULMAN C (2018) CORRELATION AND PROGNOSTIC SIGNIFICANCE OF p53, p21WAF1/CIP1 AND Ki-67 EXPRESSION IN PATIENTS WITH SUPERFICIAL BLADDER TUMORS TREATED WITH BACILLUS CALMETTE-GUERIN INTRAVESICAL THERAPYJournal of Urology, VOL. 161, NO. 3, (792-798), Online publication date: 1-Mar-1999.PFISTER C, FLAMAN J, DUNET F, GRISE P and FREBOURG T (2018) P53 MUTATIONS IN BLADDER TUMORS INACTIVATE THE TRANSACTIVATION OF THE P21 AND BAX GENES, AND HAVE A PREDICTIVE VALUE FOR THE CLINICAL OUTCOME AFTER BACILLUS CALMETTE-GUERIN THERAPYJournal of Urology, VOL. 162, NO. 1, (69-73), Online publication date: 1-Jul-1999.FONTANA D, BELLINA M, GALIETTI F, SCOFFONE C, CAGNAZZI E, GUERCIO S, CAPPIA S and POZZI E (2018) INTRAVESICAL BACILLUS CALMETTE-GUERIN (BCG) AS INDUCER OF TUMOR-SUPPRESSING PROTEINS P53 AND P21Waf1-Cip1 DURING TREATMENT OF SUPERFICIAL BLADDER CANCERJournal of Urology, VOL. 162, NO. 1, (225-230), Online publication date: 1-Jul-1999. Volume 159Issue 3March 1998Page: 788-791 Advertisement Copyright & Permissions© 1998 by American Urological Association, Inc.MetricsAuthor Information THIERRY LEBRET More articles by this author VERONIQUE BECETTE More articles by this author MICHEL BARBAGELATTA More articles by this author JEAN-MARIE HERVE More articles by this author FRANCOIS GAUDEZ More articles by this author PHILIPPE BARRE More articles by this author PIERRE-MARIE LUGAGNE More articles by this author HENRY BOTTO More articles by this author Expand All Advertisement PDF downloadLoading ...