Abstract
To understand better the role of physical p53 deletion in bladder cancer, 106 formalin-fixed and 45 unfixed bladder tumors were examined using fluorescence in situ hybridization. Probes for centromere 17 and the p53 locus were hybridized simultaneously to interphase tumor cells to analyze p53 and chromosome 17 copy number on a cell by cell basis. 17p deletion was found in four of 43 pTa tumors, 18 of 43 pT1 tumors and 29 of 58 pT2-4 tumors (P = 0.0001). 17p deletion was also highly correlated with grade (P = 0.0001) and with p53 immunostaining (P = 0.0005). Chromosome 17 polysomy was associated with stage, grade, 17p deletions, and p53 immunostaining (P = 0.0001). The strong difference in centromere 17 copy number and 17p deletions between pTa and pT1 tumors supports a relevant biological distinction between pTa and pT1 tumors.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baker S. J., Markowitz S., Fearon E. R., Willson J. K., Vogelstein B. Suppression of human colorectal carcinoma cell growth by wild-type p53. Science. 1990 Aug 24;249(4971):912–915. doi: 10.1126/science.2144057. [DOI] [PubMed] [Google Scholar]
- Bartek J., Iggo R., Gannon J., Lane D. P. Genetic and immunochemical analysis of mutant p53 in human breast cancer cell lines. Oncogene. 1990 Jun;5(6):893–899. [PubMed] [Google Scholar]
- Barton C. M., Staddon S. L., Hughes C. M., Hall P. A., O'Sullivan C., Klöppel G., Theis B., Russell R. C., Neoptolemos J., Williamson R. C. Abnormalities of the p53 tumour suppressor gene in human pancreatic cancer. Br J Cancer. 1991 Dec;64(6):1076–1082. doi: 10.1038/bjc.1991.467. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Biegel J. A., Burk C. D., Barr F. G., Emanuel B. S. Evidence for a 17p tumor related locus distinct from p53 in pediatric primitive neuroectodermal tumors. Cancer Res. 1992 Jun 15;52(12):3391–3395. [PubMed] [Google Scholar]
- Bodner S. M., Minna J. D., Jensen S. M., D'Amico D., Carbone D., Mitsudomi T., Fedorko J., Buchhagen D. L., Nau M. M., Gazdar A. F. Expression of mutant p53 proteins in lung cancer correlates with the class of p53 gene mutation. Oncogene. 1992 Apr;7(4):743–749. [PubMed] [Google Scholar]
- Bártek J., Bártková J., Vojtesek B., Stasková Z., Lukás J., Rejthar A., Kovarík J., Midgley C. A., Gannon J. V., Lane D. P. Aberrant expression of the p53 oncoprotein is a common feature of a wide spectrum of human malignancies. Oncogene. 1991 Sep;6(9):1699–1703. [PubMed] [Google Scholar]
- Cattoretti G., Rilke F., Andreola S., D'Amato L., Delia D. P53 expression in breast cancer. Int J Cancer. 1988 Feb 15;41(2):178–183. doi: 10.1002/ijc.2910410204. [DOI] [PubMed] [Google Scholar]
- Chen L. C., Neubauer A., Kurisu W., Waldman F. M., Ljung B. M., Goodson W., 3rd, Goldman E. S., Moore D., 2nd, Balazs M., Liu E. Loss of heterozygosity on the short arm of chromosome 17 is associated with high proliferative capacity and DNA aneuploidy in primary human breast cancer. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3847–3851. doi: 10.1073/pnas.88.9.3847. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cogen P. H., Daneshvar L., Metzger A. K., Duyk G., Edwards M. S., Sheffield V. C. Involvement of multiple chromosome 17p loci in medulloblastoma tumorigenesis. Am J Hum Genet. 1992 Mar;50(3):584–589. [PMC free article] [PubMed] [Google Scholar]
- Coles C., Thompson A. M., Elder P. A., Cohen B. B., Mackenzie I. M., Cranston G., Chetty U., Mackay J., Macdonald M., Nakamura Y. Evidence implicating at least two genes on chromosome 17p in breast carcinogenesis. Lancet. 1990 Sep 29;336(8718):761–763. doi: 10.1016/0140-6736(90)93236-i. [DOI] [PubMed] [Google Scholar]
- Cunningham J., Lust J. A., Schaid D. J., Bren G. D., Carpenter H. A., Rizza E., Kovach J. S., Thibodeau S. N. Expression of p53 and 17p allelic loss in colorectal carcinoma. Cancer Res. 1992 Apr 1;52(7):1974–1980. [PubMed] [Google Scholar]
- Eccles D. M., Brett L., Lessells A., Gruber L., Lane D., Steel C. M., Leonard R. C. Overexpression of the p53 protein and allele loss at 17p13 in ovarian carcinoma. Br J Cancer. 1992 Jan;65(1):40–44. doi: 10.1038/bjc.1992.8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fields S., Jang S. K. Presence of a potent transcription activating sequence in the p53 protein. Science. 1990 Aug 31;249(4972):1046–1049. doi: 10.1126/science.2144363. [DOI] [PubMed] [Google Scholar]
- Finlay C. A., Hinds P. W., Tan T. H., Eliyahu D., Oren M., Levine A. J. Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life. Mol Cell Biol. 1988 Feb;8(2):531–539. doi: 10.1128/mcb.8.2.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Flamm J., Havelec L. Factors affecting survival in primary superficial bladder cancer. Eur Urol. 1990;17(2):113–118. doi: 10.1159/000464017. [DOI] [PubMed] [Google Scholar]
- Foord O. S., Bhattacharya P., Reich Z., Rotter V. A DNA binding domain is contained in the C-terminus of wild type p53 protein. Nucleic Acids Res. 1991 Oct 11;19(19):5191–5198. doi: 10.1093/nar/19.19.5191. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frankel R. H., Bayona W., Koslow M., Newcomb E. W. p53 mutations in human malignant gliomas: comparison of loss of heterozygosity with mutation frequency. Cancer Res. 1992 Mar 15;52(6):1427–1433. [PubMed] [Google Scholar]
- Habuchi T., Ogawa O., Kakehi Y., Ogura K., Koshiba M., Sugiyama T., Yoshida O. Allelic loss of chromosome 17p in urothelial cancer: strong association with invasive phenotype. J Urol. 1992 Nov;148(5):1595–1599. doi: 10.1016/s0022-5347(17)36977-x. [DOI] [PubMed] [Google Scholar]
- Hinds P., Finlay C., Levine A. J. Mutation is required to activate the p53 gene for cooperation with the ras oncogene and transformation. J Virol. 1989 Feb;63(2):739–746. doi: 10.1128/jvi.63.2.739-746.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
- Iggo R., Gatter K., Bartek J., Lane D., Harris A. L. Increased expression of mutant forms of p53 oncogene in primary lung cancer. Lancet. 1990 Mar 24;335(8691):675–679. doi: 10.1016/0140-6736(90)90801-b. [DOI] [PubMed] [Google Scholar]
- Isobe M., Emanuel B. S., Givol D., Oren M., Croce C. M. Localization of gene for human p53 tumour antigen to band 17p13. Nature. 1986 Mar 6;320(6057):84–85. doi: 10.1038/320084a0. [DOI] [PubMed] [Google Scholar]
- Isola J., Visakorpi T., Holli K., Kallioniemi O. P. Association of overexpression of tumor suppressor protein p53 with rapid cell proliferation and poor prognosis in node-negative breast cancer patients. J Natl Cancer Inst. 1992 Jul 15;84(14):1109–1114. doi: 10.1093/jnci/84.14.1109. [DOI] [PubMed] [Google Scholar]
- Iwaya K., Tsuda H., Hiraide H., Tamaki K., Tamakuma S., Fukutomi T., Mukai K., Hirohashi S. Nuclear p53 immunoreaction associated with poor prognosis of breast cancer. Jpn J Cancer Res. 1991 Jul;82(7):835–840. doi: 10.1111/j.1349-7006.1991.tb02710.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kallioniemi O. P., Kallioniemi A., Kurisu W., Thor A., Chen L. C., Smith H. S., Waldman F. M., Pinkel D., Gray J. W. ERBB2 amplification in breast cancer analyzed by fluorescence in situ hybridization. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5321–5325. doi: 10.1073/pnas.89.12.5321. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lane D. P. Cancer. p53, guardian of the genome. Nature. 1992 Jul 2;358(6381):15–16. doi: 10.1038/358015a0. [DOI] [PubMed] [Google Scholar]
- Levine A. J. The p53 tumor suppressor gene and gene product. Princess Takamatsu Symp. 1989;20:221–230. [PubMed] [Google Scholar]
- Marks J. R., Davidoff A. M., Kerns B. J., Humphrey P. A., Pence J. C., Dodge R. K., Clarke-Pearson D. L., Iglehart J. D., Bast R. C., Jr, Berchuck A. Overexpression and mutation of p53 in epithelial ovarian cancer. Cancer Res. 1991 Jun 1;51(11):2979–2984. [PubMed] [Google Scholar]
- Matsumura K., Kallioniemi A., Kallioniemi O., Chen L., Smith H. S., Pinkel D., Gray J., Waldman F. M. Deletion of chromosome 17p loci in breast cancer cells detected by fluorescence in situ hybridization. Cancer Res. 1992 Jun 15;52(12):3474–3477. [PubMed] [Google Scholar]
- Meltzer S. J., Yin J., Huang Y., McDaniel T. K., Newkirk C., Iseri O., Vogelstein B., Resau J. H. Reduction to homozygosity involving p53 in esophageal cancers demonstrated by the polymerase chain reaction. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4976–4980. doi: 10.1073/pnas.88.11.4976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller C. W., Simon K., Aslo A., Kok K., Yokota J., Buys C. H., Terada M., Koeffler H. P. p53 mutations in human lung tumors. Cancer Res. 1992 Apr 1;52(7):1695–1698. [PubMed] [Google Scholar]
- Milner J., Medcalf E. A. Cotranslation of activated mutant p53 with wild type drives the wild-type p53 protein into the mutant conformation. Cell. 1991 May 31;65(5):765–774. doi: 10.1016/0092-8674(91)90384-b. [DOI] [PubMed] [Google Scholar]
- Mørkve O., Laerum O. D. Flow cytometric measurement of p53 protein expression and DNA content in paraffin-embedded tissue from bronchial carcinomas. Cytometry. 1991;12(5):438–444. doi: 10.1002/cyto.990120509. [DOI] [PubMed] [Google Scholar]
- Olumi A. F., Tsai Y. C., Nichols P. W., Skinner D. G., Cain D. R., Bender L. I., Jones P. A. Allelic loss of chromosome 17p distinguishes high grade from low grade transitional cell carcinomas of the bladder. Cancer Res. 1990 Nov 1;50(21):7081–7083. [PubMed] [Google Scholar]
- Purdie C. A., O'Grady J., Piris J., Wyllie A. H., Bird C. C. p53 expression in colorectal tumors. Am J Pathol. 1991 Apr;138(4):807–813. [PMC free article] [PubMed] [Google Scholar]
- Raghavan D., Shipley W. U., Garnick M. B., Russell P. J., Richie J. P. Biology and management of bladder cancer. N Engl J Med. 1990 Apr 19;322(16):1129–1138. doi: 10.1056/NEJM199004193221607. [DOI] [PubMed] [Google Scholar]
- Sarkis A. S., Dalbagni G., Cordon-Cardo C., Zhang Z. F., Sheinfeld J., Fair W. R., Herr H. W., Reuter V. E. Nuclear overexpression of p53 protein in transitional cell bladder carcinoma: a marker for disease progression. J Natl Cancer Inst. 1993 Jan 6;85(1):53–59. doi: 10.1093/jnci/85.1.53. [DOI] [PubMed] [Google Scholar]
- Scott N., Sagar P., Stewart J., Blair G. E., Dixon M. F., Quirke P. p53 in colorectal cancer: clinicopathological correlation and prognostic significance. Br J Cancer. 1991 Feb;63(2):317–319. doi: 10.1038/bjc.1991.74. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sidransky D., Von Eschenbach A., Tsai Y. C., Jones P., Summerhayes I., Marshall F., Paul M., Green P., Hamilton S. R., Frost P. Identification of p53 gene mutations in bladder cancers and urine samples. Science. 1991 May 3;252(5006):706–709. doi: 10.1126/science.2024123. [DOI] [PubMed] [Google Scholar]
- Thompson A. M., Anderson T. J., Condie A., Prosser J., Chetty U., Carter D. C., Evans H. J., Steel C. M. p53 allele losses, mutations and expression in breast cancer and their relationship to clinico-pathological parameters. Int J Cancer. 1992 Feb 20;50(4):528–532. doi: 10.1002/ijc.2910500405. [DOI] [PubMed] [Google Scholar]
- Thor A. D., Moore DH I. I., Edgerton S. M., Kawasaki E. S., Reihsaus E., Lynch H. T., Marcus J. N., Schwartz L., Chen L. C., Mayall B. H. Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers. J Natl Cancer Inst. 1992 Jun 3;84(11):845–855. doi: 10.1093/jnci/84.11.845. [DOI] [PubMed] [Google Scholar]
- Tsai Y. C., Nichols P. W., Hiti A. L., Williams Z., Skinner D. G., Jones P. A. Allelic losses of chromosomes 9, 11, and 17 in human bladder cancer. Cancer Res. 1990 Jan 1;50(1):44–47. [PubMed] [Google Scholar]
- Varley J. M., Brammar W. J., Lane D. P., Swallow J. E., Dolan C., Walker R. A. Loss of chromosome 17p13 sequences and mutation of p53 in human breast carcinomas. Oncogene. 1991 Mar;6(3):413–421. [PubMed] [Google Scholar]
- Waldman F. M., Carroll P. R., Cohen M. B., Kerschmann R., Chew K., Mayall B. H. 5-Bromodeoxyuridine incorporation and PCNA expression as measures of cell proliferation in transitional cell carcinoma of the urinary bladder. Mod Pathol. 1993 Jan;6(1):20–24. [PubMed] [Google Scholar]
- Weinberg R. A. Tumor suppressor genes. Science. 1991 Nov 22;254(5035):1138–1146. doi: 10.1126/science.1659741. [DOI] [PubMed] [Google Scholar]
- Wright C., Mellon K., Johnston P., Lane D. P., Harris A. L., Horne C. H., Neal D. E. Expression of mutant p53, c-erbB-2 and the epidermal growth factor receptor in transitional cell carcinoma of the human urinary bladder. Br J Cancer. 1991 Jun;63(6):967–970. doi: 10.1038/bjc.1991.211. [DOI] [PMC free article] [PubMed] [Google Scholar]