FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 331:1259-1264 November 10, 1994 Number 19 Next

	Full Text Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background We have previously demonstrated a strong association between nuclear accumulation of p53 protein, as determined by immunohistochemical analysis, and mutations in the p53 gene. The purpose of this study was to determine the relation between nuclear accumulation of p53 and tumor progression in transitional-cell carcinoma of the bladder.

Methods Histologic specimens of transitional-cell carcinoma of the bladder (stages Pa, noninvasive disease, to P4, disease with direct extension into adjacent organs or structures) from 243 patients who were treated by radical cystectomy were examined for the immunohistochemical detection of p53 protein. Nuclear p53 reactivity was then analyzed in relation to time to recurrence and overall survival.

Results The detection of nuclear p53 was significantly associated with an increased risk of recurrence of bladder cancer (P<0.001) and with decreased overall survival (P<0.001). In patients with cancer confined to the bladder, the rates of recurrence for stage P1, P2, and P3a tumors that had no detectable nuclear p53 reactivity at five years were 7, 12, and 11 percent, respectively, as compared with 62, 56, and 80 percent, respectively, for tumors that had p53 immunoreactivity. Similar results were obtained when the presence or absence of p53 in the nuclei of the tumor cells was studied in relation to overall survival. In a multivariable analysis stratified according to grade, pathological stage, and lymph-node status, nuclear p53 status was an independent predictor (and in cancer confined to the bladder, the only independent predictor) of recurrence and overall survival (P<0.001).

Conclusions In patients with transitional-cell carcinoma confined to the bladder, an accumulation of p53 in the tumor-cell nuclei detected by immunohistochemical methods predicts a significantly increased risk of recurrence and death, independently of tumor grade, stage, and lymph-node status. Patients with transitional-cell carcinoma confined to the bladder that demonstrates nuclear p53 reactivity should be considered for protocols of adjuvant treatment.

Source Information

From the Departments of Urology (D. Esrig, D. Elmajian, J.A.F., J.P.S., D.G.S., P.A.J.), Preventive Medicine (S.G., S.-C.C.), and Pathology (P.W.N., R.J.C.), University of Southern California School of Medicine and Kenneth Norris Jr. Comprehensive Cancer Center, Los Angeles.

Address reprint requests to Dr. Cote at the Department of Pathology, University of Southern California School of Medicine, Kenneth Norris Jr. Cancer Center, 1441 Eastlake Ave., Los Angeles, CA 90033.

Full Text of this Article

Related Letters:

p53 and Bladder Cancer
Li W. W., Li V. W., Tsakayannis D., Xing X., Wood L. L., Cote R. J., Skinner D. G., Jones P. A.
Extract | Full Text  
N Engl J Med 1995; 332:957-958, Apr 6, 1995. Correspondence

This article has been cited by other articles:

• Rosenberg, J. E., Hahn, W. C. (2009). Bladder cancer: modeling and translation. Genes Dev. 23: 655-659 [Abstract] [Full Text]  
• Puzio-Kuter, A. M., Castillo-Martin, M., Kinkade, C. W., Wang, X., Shen, T. H., Matos, T., Shen, M. M., Cordon-Cardo, C., Abate-Shen, C. (2009). Inactivation of p53 and Pten promotes invasive bladder cancer. Genes Dev. 23: 675-680 [Abstract] [Full Text]  
• Das, D., Wojno, K., Imperiale, M. J. (2008). BK Virus as a Cofactor in the Etiology of Prostate Cancer in Its Early Stages. J. Virol. 82: 2705-2714 [Abstract] [Full Text]  
• Real, F. X. (2007). p53: It Has It All, But Will It Make It to the Clinic As a Marker in Bladder Cancer?. JCO 25: 5341-5344 [Full Text]  
• George, B., Datar, R. H., Wu, L., Cai, J., Patten, N., Beil, S. J., Groshen, S., Stein, J., Skinner, D., Jones, P. A., Cote, R. J. (2007). p53 Gene and Protein Status: The Role of p53 Alterations in Predicting Outcome in Patients With Bladder Cancer. JCO 25: 5352-5358 [Abstract] [Full Text]  
• Iida, K., Itoh, K., Maher, J. M., Kumagai, Y., Oyasu, R., Mori, Y., Shimazui, T., Akaza, H., Yamamoto, M. (2007). Nrf2 and p53 cooperatively protect against BBN-induced urinary bladder carcinogenesis. Carcinogenesis 28: 2398-2403 [Abstract] [Full Text]  
• Bellmunt, J, Paz-Ares, L, Cuello, M, Cecere, F., Albiol, S, Guillem, V, Gallardo, E, Carles, J, Mendez, P, de la Cruz, J., Taron, M, Rosell, R, Baselga, J, On behalf of Spanish Oncology Genitourinary Group, (2007). Gene expression of ERCC1 as a novel prognostic marker in advanced bladder cancer patients receiving cisplatin-based chemotherapy. Ann Oncol 18: 522-528 [Abstract] [Full Text]  
• Urushibara, M., Kageyama, Y., Akashi, T., Otsuka, Y., Takizawa, T., Koike, M., Kihara, K. (2007). HSP60 may Predict Good Pathological Response to Neoadjuvant Chemoradiotherapy in Bladder Cancer. Jpn J Clin Oncol 37: 56-61 [Abstract] [Full Text]  
• Mitra, A. P., Datar, R. H., Cote, R. J. (2006). Molecular Pathways in Invasive Bladder Cancer: New Insights Into Mechanisms, Progression, and Target Identification. JCO 24: 5552-5564 [Abstract] [Full Text]  
• Lopez-Knowles, E., Hernandez, S., Kogevinas, M., Lloreta, J., Amoros, A., Tardon, A., Carrato, A., Kishore, S., Serra, C., Malats, N., Real, F. X., on behalf of the EPICURO Study Investigators, (2006). The p53 Pathway and Outcome among Patients with T1G3 Bladder Tumors.. Clin. Cancer Res. 12: 6029-6036 [Abstract] [Full Text]  
• Sawhney, R, Bourgeois, D, Chaudhary, U. (2006). Neo-adjuvant chemotherapy for muscle-invasive bladder cancer: a look ahead. Ann Oncol 17: 1360-1369 [Abstract] [Full Text]  
• Hernandez, S., Lopez-Knowles, E., Lloreta, J., Kogevinas, M., Amoros, A., Tardon, A., Carrato, A., Serra, C., Malats, N., Real, F. X. (2006). Prospective Study of FGFR3 Mutations As a Prognostic Factor in Nonmuscle Invasive Urothelial Bladder Carcinomas. JCO 24: 3664-3671 [Abstract] [Full Text]  
• Cohen, S. M., Goel, A., Phillips, J., Ennis, R. D., Grossbard, M. L. (2006). The Role of Perioperative Chemotherapy in the Treatment of Urothelial Cancer. The Oncologist 11: 630-640 [Abstract] [Full Text]  
• Ishimura, H., Takahashi, T., Nakagawa, H., Nishimura, S.-I., Arai, Y., Horikawa, Y., Habuchi, T., Miyoshi, E., Kyan, A., Hagisawa, S., Ohyama, C. (2006). N-Acetylglucosaminyltransferase V and {beta}1-6 Branching N-Linked Oligosaccharides Are Associated with Good Prognosis of Patients with Bladder Cancer. Clin. Cancer Res. 12: 2506-2511 [Abstract] [Full Text]  
• Knowles, M. A. (2006). Molecular subtypes of bladder cancer: Jekyll and Hyde or chalk and cheese?. Carcinogenesis 27: 361-373 [Abstract] [Full Text]  
• Quintero, A, Alvarez-Kindelan, J, Luque, R J, Gonzalez-Campora, R, Requena, M J, Montironi, R, Lopez-Beltran, A (2006). Ki-67 MIB1 labelling index and the prognosis of primary TaT1 urothelial cell carcinoma of the bladder. J. Clin. Pathol. 59: 83-88 [Abstract] [Full Text]  
• Marsit, C. J., Karagas, M. R., Andrew, A., Liu, M., Danaee, H., Schned, A. R., Nelson, H. H., Kelsey, K. T. (2005). Epigenetic Inactivation of SFRP Genes and TP53 Alteration Act Jointly as Markers of Invasive Bladder Cancer. Cancer Res. 65: 7081-7085 [Abstract] [Full Text]  
• Hernandez, S., Lopez-Knowles, E., Lloreta, J., Kogevinas, M., Jaramillo, R., Amoros, A., Tardon, A., Garcia-Closas, R., Serra, C., Carrato, A., Malats, N., Real, F. X. (2005). FGFR3 and Tp53 Mutations in T1G3 Transitional Bladder Carcinomas: Independent Distribution and Lack of Association with Prognosis. Clin. Cancer Res. 11: 5444-5450 [Abstract] [Full Text]  
• Zi, X., Simoneau, A. R. (2005). Flavokawain A, a Novel Chalcone from Kava Extract, Induces Apoptosis in Bladder Cancer Cells by Involvement of Bax Protein-Dependent and Mitochondria-Dependent Apoptotic Pathway and Suppresses Tumor Growth in Mice. Cancer Res. 65: 3479-3486 [Abstract] [Full Text]  
• Frey, U. H., Eisenhardt, A., Lummen, G., Rubben, H., Jockel, K.-H., Schmid, K. W., Siffert, W. (2005). The T393C Polymorphism of the G{alpha}s Gene (GNAS1) Is a Novel Prognostic Marker in Bladder Cancer. Cancer Epidemiol. Biomarkers Prev. 14: 871-877 [Abstract] [Full Text]  
• Takata, R., Katagiri, T., Kanehira, M., Tsunoda, T., Shuin, T., Miki, T., Namiki, M., Kohri, K., Matsushita, Y., Fujioka, T., Nakamura, Y. (2005). Predicting Response to Methotrexate, Vinblastine, Doxorubicin, and Cisplatin Neoadjuvant Chemotherapy for Bladder Cancers through Genome-Wide Gene Expression Profiling. Clin. Cancer Res. 11: 2625-2636 [Abstract] [Full Text]  
• Goebell, P. J., Groshen, S., Schmitz-Drager, B. J., Sylvester, R., Kogevinas, M., Malats, N., Sauter, G., Grossman, H. B., Dinney, C. P.N., Waldman, F., Cote, R. J. (2005). Concepts for Banking Tissue in Urologic Oncology--The International Bladder Cancer Bank. Clin. Cancer Res. 11: 413-415 [Full Text]  
• Schultz, I. J., Kiemeney, L. A., Karthaus, H. F.M., Witjes, J. A., Willems, J. L., Swinkels, D. W., Gunnewiek, J. M.T. K., de Kok, J. B. (2004). Survivin mRNA Copy Number in Bladder Washings Predicts Tumor Recurrence in Patients with Superficial Urothelial Cell Carcinomas. Clin. Chem. 50: 1425-1428 [Full Text]  
• Kawamura, K., Izumi, H., Ma, Z., Ikeda, R., Moriyama, M., Tanaka, T., Nojima, T., Levin, L. S., Fujikawa-Yamamoto, K., Suzuki, K., Fukasawa, K. (2004). Induction of Centrosome Amplification and Chromosome Instability in Human Bladder Cancer Cells by p53 Mutation and Cyclin E Overexpression. Cancer Res. 64: 4800-4809 [Abstract] [Full Text]  
• Shariat, S. F., Tokunaga, H., Zhou, J., Kim, J., Ayala, G. E., Benedict, W. F., Lerner, S. P. (2004). p53, p21, pRB, and p16 Expression Predict Clinical Outcome in Cystectomy With Bladder Cancer. JCO 22: 1014-1024 [Abstract] [Full Text]  
• Chatterjee, S. J., Datar, R., Youssefzadeh, D., George, B., Goebell, P. J., Stein, J. P., Young, L., Shi, S.-R., Gee, C., Groshen, S., Skinner, D. G., Cote, R. J. (2004). Combined Effects of p53, p21, and pRb Expression in the Progression of Bladder Transitional Cell Carcinoma. JCO 22: 1007-1013 [Abstract] [Full Text]  
• Catto, J. W. F., Linkens, D. A., Abbod, M. F., Chen, M., Burton, J. L., Feeley, K. M., Hamdy, F. C. (2003). Artificial Intelligence in Predicting Bladder Cancer Outcome: A Comparison of Neuro-Fuzzy Modeling and Artificial Neural Networks. Clin. Cancer Res. 9: 4172-4177 [Abstract] [Full Text]  
• Pagliaro, L. C., Keyhani, A., Williams, D., Woods, D., Liu, B., Perrotte, P., Slaton, J. W., Merritt, J. A., Grossman, H. B., Dinney, C. P. (2003). Repeated Intravesical Instillations of an Adenoviral Vector in Patients With Locally Advanced Bladder Cancer: A Phase I Study of p53 Gene Therapy. JCO 21: 2247-2253 [Abstract] [Full Text]  
• Loukopoulos, P., Thornton, J. R., Robinson, W. F. (2003). Clinical and Pathologic Relevance of p53 Index in Canine Osseous Tumors. Vet Pathol 40: 237-248 [Abstract] [Full Text]  
• Derenzini, M., Montanaro, L., Chilla, A., Tosti, E., Ceccarelli, C., Dall'Olio, F., Ofner, D., Trere, D. (2002). Evaluation of Thymidylate Synthase Protein Expression by Western Blotting and Immunohistochemistry on Human Colon Carcinoma Xenografts in Nude Mice. J. Histochem. Cytochem. 50: 1633-1640 [Abstract] [Full Text]  
• Stoeber, K., Swinn, R., Prevost, A. T., de Clive-Lowe, P., Halsall, I., Dilworth, S. M., Marr, J., Turner, W. H., Bullock, N., Doble, A., Hales, C. N., Williams, G. H. (2002). Diagnosis of Genito-Urinary Tract Cancer by Detection of Minichromosome Maintenance 5 Protein in Urine Sediments. JNCI J Natl Cancer Inst 94: 1071-1079 [Abstract] [Full Text]  
• Lin, H-J, Chen, W-C, Tsai, F-J, Tsai, S-W (2002). Distributions of p53 codon 72 polymorphism in primary open angle glaucoma. Br J Ophthalmol 86: 767-770 [Abstract] [Full Text]  
• Cheng, H.-L., Trink, B., Tzai, T.-S., Liu, H.-S., Chan, S.-H., Ho, C.-L., Sidransky, D., Chow, N.-H. (2002). Overexpression of c-met as a Prognostic Indicator for Transitional Cell Carcinoma of the Urinary Bladder: A Comparison With p53 Nuclear Accumulation. JCO 20: 1544-1550 [Abstract] [Full Text]  
• Kuball, J., Wen, S. F., Leissner, J., Atkins, D., Meinhardt, P., Quijano, E., Engler, H., Hutchins, B., Maneval, D. C., Grace, M. J., Fritz, M. A., Storkel, S., Thuroff, J. W., Huber, C., Schuler, M. (2002). Successful Adenovirus-Mediated Wild-Type p53 Gene Transfer in Patients With Bladder Cancer by Intravesical Vector Instillation. JCO 20: 957-965 [Abstract] [Full Text]  
• Pollack, I. F., Finkelstein, S. D., Woods, J., Burnham, J., Holmes, E. J., Hamilton, R. L., Yates, A. J., Boyett, J. M., Finlay, J. L., Sposto, R., the Children's Cancer Group, (2002). Expression of p53 and Prognosis in Children with Malignant Gliomas. NEJM 346: 420-427 [Abstract] [Full Text]  
• Murphy, W. M. (2002). Human Carcinogenesis, the New Genetics, and the Practicing Pathologist. INT J SURG PATHOL 10: 1-5 [Abstract]  
• Lu, M.-L., Wikman, F., Orntoft, T. F., Charytonowicz, E., Rabbani, F., Zhang, Z., Dalbagni, G., Pohar, K. S., Yu, G., Cordon-Cardo, C. (2002). Impact of Alterations Affecting the p53 Pathway in Bladder Cancer on Clinical Outcome, Assessed by Conventional and Array-based Methods. Clin. Cancer Res. 8: 171-179 [Abstract] [Full Text]  
• Latronico, A. C., Pinto, E. M., Domenice, S., Fragoso, M. C. B. V., Martin, R. M., Zerbini, M. C., Lucon, A. M., Mendonca, B. B. (2001). An Inherited Mutation Outside the Highly Conserved DNA-Binding Domain of the p53 Tumor Suppressor Protein in Children and Adults with Sporadic Adrenocortical Tumors. J. Clin. Endocrinol. Metab. 86: 4970-4973 [Abstract] [Full Text]  
• Pollack, I. F., Finkelstein, S. D., Burnham, J., Holmes, E. J., Hamilton, R. L., Yates, A. J., Finlay, J. L., Sposto, R. (2001). Age and TP53 Mutation Frequency in Childhood Malignant Gliomas: Results in a Multi-institutional Cohort. Cancer Res. 61: 7404-7407 [Abstract] [Full Text]  
• Knowles, M A (2001). What we could do now: molecular pathology of bladder cancer. Mol. Pathol. 54: 215-221 [Abstract] [Full Text]  
• Inoue, K., Slaton, J. W., Karashima, T., Yoshikawa, C., Shuin, T., Sweeney, P., Millikan, R., Dinney, C. P. N. (2000). The Prognostic Value of Angiogenesis Factor Expression for Predicting Recurrence and Metastasis of Bladder Cancer after Neoadjuvant Chemotherapy and Radical Cystectomy. Clin. Cancer Res. 6: 4866-4873 [Abstract] [Full Text]  
• Schneider, A., Borgnat, S., Lang, H., Régine, O., Lindner, V., Kassem, M., Saussine, C., Oudet, P., Jacqmin, D., Gaub, M. P. (2000). Evaluation of Microsatellite Analysis in Urine Sediment for Diagnosis of Bladder Cancer. Cancer Res. 60: 4617-4622 [Abstract] [Full Text]  
• McShane, L. M., Aamodt, R., Cordon-Cardo, C., Cote, R., Faraggi, D., Fradet, Y., Grossman, H. B., Peng, A., Taube, S. E., Waldman, F. M., Network, t. N. C. I. B. T. M. (2000). Reproducibility of p53 Immunohistochemistry in Bladder Tumors. Clin. Cancer Res. 6: 1854-1864 [Abstract] [Full Text]  
• LaRue, H., Allard, P., Simoneau, M., Normand, C., Pfister, C., Moore, L., Meyer, F., Tetu, B., Fradet, Y. (2000). P53 point mutations in initial superficial bladder cancer occur only in tumors from current or recent cigarette smokers. Carcinogenesis 21: 101-106 [Abstract] [Full Text]  
• Krasna, M. J., Mao, Y. S., Sonett, J. R., Tamura, G., Jones, R., Suntharalingam, M., Meltzer, S. J. (1999). P53 gene protein overexpression predicts results of trimodality therapy in esophageal cancer patients. Ann. Thorac. Surg. 68: 2021-2024 [Abstract] [Full Text]  
• Qureshi, K. N., Griffiths, T. R. L., Robinson, M. C., Marsh, C., Roberts, J. T., Hall, R. R., Lunec, J., Neal, D. E. (1999). TP53 Accumulation Predicts Improved Survival in Patients Resistant to Systemic Cisplatin-based Chemotherapy forMuscle-invasive Bladder Cancer. Clin. Cancer Res. 5: 3500-3507 [Abstract] [Full Text]  
• Del Pizzo, J. J., Borkowski, A., Jacobs, S. C., Kyprianou, N. (1999). Loss of Cell Cycle Regulators p27Kip1 and Cyclin E in Transitional Cell Carcinoma of the Bladder Correlates with Tumor Grade and Patient Survival. Am. J. Pathol. 155: 1129-1136 [Abstract] [Full Text]  
• Lee, C. C. R., Ichihara, T., Yamamoto, S., Wanibuchi, H., Sugimura, K., Wada, S., Kishimoto, T., Fukushima, S. (1999). Reduced expression of the CDK inhibitor p27KIP1 in rat two-stage bladder carcinogenesis and its association with expression profiles of p21WAF1/Cip1 and p53. Carcinogenesis 20: 1697-1708 [Abstract] [Full Text]  
• PEI, Y., WATNICK, T., HE, N., WANG, K., LIANG, Y., PARFREY, P., GERMINO, G., GEORGE-HYSLOP, P. ST. (1999). Somatic PKD2 Mutations in Individual Kidney and Liver Cysts Support a "Two-Hit" Model of Cystogenesis in Type 2 Autosomal Dominant Polycystic Kidney Disease. J. Am. Soc. Nephrol. 10: 1524-1529 [Abstract] [Full Text]  
• Yeager, T. R., DeVries, S., Jarrard, D. F., Kao, C., Nakada, S. Y., Moon, T. D., Bruskewitz, R., Stadler, W. M., Meisner, L. F., Gilchrist, K. W., Newton, M. A., Waldman, F. M., Reznikoff, C. A. (1998). Overcoming cellular senescence in human cancer pathogenesis. Genes Dev. 12: 163-174 [Abstract] [Full Text]  
• Shpitzer, T., Chaimoff, M., Gal, R., Stern, Y., Feinmesser, R., Segal, K. (1996). Tumor Angiogenesis as a Prognostic Factor in Early Oral Tongue Cancer. Arch Otolaryngol Head Neck Surg 122: 865-868 [Abstract]  
• Albertsen, P. C. (1996). Urology. JAMA 275: 1857-1858 [Abstract]  
• Li, W. W., Li, V. W., Tsakayannis, D., Xing, X., Wood, L. L., Cote, R. J., Skinner, D. G., Jones, P. A. (1995). p53 and Bladder Cancer. NEJM 332: 957-958 [Full Text]