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. 1995 Jan;71(1):201–205. doi: 10.1038/bjc.1995.41

p53 immunohistochemistry as an independent prognostic factor for superficial transitional cell carcinoma of the bladder.

J Serth 1, M A Kuczyk 1, C Bokemeyer 1, C Hervatin 1, R Nafe 1, H K Tan 1, U Jonas 1
PMCID: PMC2033435  PMID: 7819040

Abstract

Although patients with superficial bladder cancer (Ta, T1) have a generally good prognosis, those patients who develop muscle-invasive tumours or metastatic disease at recurrence do poorly clinically. In the current study 69 patients undergoing complete transurethral resection for superficial transitional cell cancer of the bladder were investigated for different clinical and biological characteristics as possible prognostic factors: age, sex, performance of instillation therapy and immunohistochemical determination of mutational inactivation of p53 tumour-suppressor gene (monoclonal antibody PAb 1801) as well as immunohistochemical determination of the proliferation rate by staining for PCNA (proliferating cell nuclear antigen) (monoclonal antibody PC 10). After a median follow-up of 45.8 months, 12 of 14 patients (85.7%) with more than 20% of cells positive for p53 had disease progression with muscle-invasive growth compared with only one of 55 patients (1.8%) negative for p53 (P < 0.01, chi 2 test). During univariate analysis histological grade (G1 vs G2) (P = 0.0373), positivity for PCNA (> 60% of cells) (P = 0.0033) and positivity for p53 (P < 0.001) were significant prognostic factors for disease progression (log-rank test), while during multivariate analysis only positivity for p53 was a significant predictor for relapse of bladder cancer (P = 0.0029) (multivariate Cox regression analysis). The immunohistochemical detection of mutations of the p53 gene has been demonstrated to be a reliable, easily performed and thereby widely available technique for the investigation of fresh-frozen or paraffin-embedded tumour specimens. The results demonstrate the important role of the p53 tumour-suppressor gene protein in the development and for the progression of bladder cancer. If the high prognostic value of p53 mutations in superficial bladder cancer is confirmed in larger prospective trials, more aggressive therapeutic strategies could be discussed for patients with p53 mutations in their tumour specimens.

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Selected References

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  1. Banks L., Matlashewski G., Crawford L. Isolation of human-p53-specific monoclonal antibodies and their use in the studies of human p53 expression. Eur J Biochem. 1986 Sep 15;159(3):529–534. doi: 10.1111/j.1432-1033.1986.tb09919.x. [DOI] [PubMed] [Google Scholar]
  2. Bischoff J. R., Friedman P. N., Marshak D. R., Prives C., Beach D. Human p53 is phosphorylated by p60-cdc2 and cyclin B-cdc2. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4766–4770. doi: 10.1073/pnas.87.12.4766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Borland R. N., Brendler C. B., Isaacs W. B. Molecular biology of bladder cancer. Hematol Oncol Clin North Am. 1992 Feb;6(1):31–39. [PubMed] [Google Scholar]
  4. Finlay C. A., Hinds P. W., Levine A. J. The p53 proto-oncogene can act as a suppressor of transformation. Cell. 1989 Jun 30;57(7):1083–1093. doi: 10.1016/0092-8674(89)90045-7. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Gazdar A. F. Molecular markers for the diagnosis and prognosis of lung cancer. Cancer. 1992 Mar 15;69(6 Suppl):1592–1599. doi: 10.1002/1097-0142(19920315)69:6+<1592::aid-cncr2820691315>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
  7. Gerdes J. Ki-67 and other proliferation markers useful for immunohistological diagnostic and prognostic evaluations in human malignancies. Semin Cancer Biol. 1990 Jun;1(3):199–206. [PubMed] [Google Scholar]
  8. Hamilton S. R. Molecular genetics of colorectal carcinoma. Cancer. 1992 Sep 1;70(5 Suppl):1216–1221. doi: 10.1002/1097-0142(19920901)70:3+<1216::aid-cncr2820701505>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  9. Harris A. L. p53 expression in human breast cancer. Adv Cancer Res. 1992;59:69–88. doi: 10.1016/s0065-230x(08)60303-6. [DOI] [PubMed] [Google Scholar]
  10. Harris C. C., Hollstein M. Clinical implications of the p53 tumor-suppressor gene. N Engl J Med. 1993 Oct 28;329(18):1318–1327. doi: 10.1056/NEJM199310283291807. [DOI] [PubMed] [Google Scholar]
  11. Hofstädter F., Delgado R., Jakse G., Judmaier W. Urothelial dysplasia and carcinoma in situ of the bladder. Cancer. 1986 Jan 15;57(2):356–361. doi: 10.1002/1097-0142(19860115)57:2<356::aid-cncr2820570228>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
  12. Horak E., Smith K., Bromley L., LeJeune S., Greenall M., Lane D., Harris A. L. Mutant p53, EGF receptor and c-erbB-2 expression in human breast cancer. Oncogene. 1991 Dec;6(12):2277–2284. [PubMed] [Google Scholar]
  13. Jenkins J. R., Rudge K., Currie G. A. Cellular immortalization by a cDNA clone encoding the transformation-associated phosphoprotein p53. Nature. 1984 Dec 13;312(5995):651–654. doi: 10.1038/312651a0. [DOI] [PubMed] [Google Scholar]
  14. Lane D. P., Crawford L. V. T antigen is bound to a host protein in SV40-transformed cells. Nature. 1979 Mar 15;278(5701):261–263. doi: 10.1038/278261a0. [DOI] [PubMed] [Google Scholar]
  15. Lipponen P. K., Eskelinen M. J. Cell proliferation of transitional cell bladder cancer determined by PCNA/cyclin immunostaining. A histopathological description. Anticancer Res. 1992 Mar-Apr;12(2):577–583. [PubMed] [Google Scholar]
  16. Lipponen P. K., Eskelinen M. J. Cell proliferation of transitional cell bladder tumours determined by PCNA/cyclin immunostaining and its prognostic value. Br J Cancer. 1992 Jul;66(1):171–176. doi: 10.1038/bjc.1992.237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Logothetis C. J., Xu H. J., Ro J. Y., Hu S. X., Sahin A., Ordonez N., Benedict W. F. Altered expression of retinoblastoma protein and known prognostic variables in locally advanced bladder cancer. J Natl Cancer Inst. 1992 Aug 19;84(16):1256–1261. doi: 10.1093/jnci/84.16.1256. [DOI] [PubMed] [Google Scholar]
  18. Pocock R. D., Ponder B. A., O'Sullivan J. P., Ibrahim S. K., Easton D. F., Shearer R. J. Prognostic factors in non-infiltrating carcinoma of the bladder: a preliminary report. Br J Urol. 1982 Dec;54(6):711–715. doi: 10.1111/j.1464-410x.1982.tb13631.x. [DOI] [PubMed] [Google Scholar]
  19. Quinlan D. C., Davidson A. G., Summers C. L., Warden H. E., Doshi H. M. Accumulation of p53 protein correlates with a poor prognosis in human lung cancer. Cancer Res. 1992 Sep 1;52(17):4828–4831. [PubMed] [Google Scholar]
  20. 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]
  21. Sidransky D., Frost P., Von Eschenbach A., Oyasu R., Preisinger A. C., Vogelstein B. Clonal origin bladder cancer. N Engl J Med. 1992 Mar 12;326(11):737–740. doi: 10.1056/NEJM199203123261104. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Spruck C. H., 3rd, Rideout W. M., 3rd, Olumi A. F., Ohneseit P. F., Yang A. S., Tsai Y. C., Nichols P. W., Horn T., Hermann G. G., Steven K. Distinct pattern of p53 mutations in bladder cancer: relationship to tobacco usage. Cancer Res. 1993 Mar 1;53(5):1162–1166. [PubMed] [Google Scholar]
  24. Starzynska T., Bromley M., Ghosh A., Stern P. L. Prognostic significance of p53 overexpression in gastric and colorectal carcinoma. Br J Cancer. 1992 Sep;66(3):558–562. doi: 10.1038/bjc.1992.314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Summers J. L., Coon J. S., Ward R. M., Falor W. H., Miller A. W., 3rd, Weinstein R. S. Prognosis in carcinoma of the urinary bladder based upon tissue blood group abh and Thomsen-Friedenreich antigen status and karyotype of the initial tumor. Cancer Res. 1983 Feb;43(2):934–939. [PubMed] [Google Scholar]
  26. 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]
  27. Torti F. M., Lum B. L. Superficial bladder cancer. Risk of recurrence and potential role for interferon therapy. Cancer. 1987 Feb 1;59(3 Suppl):613–616. doi: 10.1002/1097-0142(19870201)59:3+<613::aid-cncr2820591307>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  28. Tubiana M., Courdi A. Cell proliferation kinetics in human solid tumors: relation to probability of metastatic dissemination and long-term survival. Radiother Oncol. 1989 May;15(1):1–18. doi: 10.1016/0167-8140(89)90113-8. [DOI] [PubMed] [Google Scholar]
  29. Visakorpi T., Kallioniemi O. P., Heikkinen A., Koivula T., Isola J. Small subgroup of aggressive, highly proliferative prostatic carcinomas defined by p53 accumulation. J Natl Cancer Inst. 1992 Jun 3;84(11):883–887. doi: 10.1093/jnci/84.11.883. [DOI] [PubMed] [Google Scholar]
  30. Waseem N. H., Lane D. P. Monoclonal antibody analysis of the proliferating cell nuclear antigen (PCNA). Structural conservation and the detection of a nucleolar form. J Cell Sci. 1990 May;96(Pt 1):121–129. doi: 10.1242/jcs.96.1.121. [DOI] [PubMed] [Google Scholar]
  31. 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]

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