Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1992 Sep;66(3):558–562. doi: 10.1038/bjc.1992.314

Prognostic significance of p53 overexpression in gastric and colorectal carcinoma.

T Starzynska 1, M Bromley 1, A Ghosh 1, P L Stern 1
PMCID: PMC1977927  PMID: 1520594

Abstract

p53 expression was examined in 55 gastric and 107 colorectal carcinomas with an immunoperoxidase technique, using the polyclonal antibody CM1 on routinely fixed, paraffin embedded tissue. p53 protein was detected in 47% gastric and in 46% colorectal carcinomas and found to correlate with stage of disease and unfavourable clinical outcome (P less than 0.001). Thus, the proportion of positively reacting neoplasms increased as the stage progressed, tumours which had invaded regional lymph-nodes overexpressed p53 more frequently than localised carcinomas and an elevated level of p53 was associated with early relapse and death. In colorectal carcinoma p53 positivity was also linked with site and macroscopic configuration of the primary tumour and was most frequently expressed in carcinomas from the rectum and in ulcerative tumours. p53 overexpression was irrespective of tumour grade. Uniform negative reactivity with anti-p53 antibody was seen in normal epithelium adjacent to carcinoma, intestinal metaplasia, atrophic gastritis and in colonic adenomas. There was a good correlation between immunohistochemical staining on paraffin and frozen sections. These studies suggest that in gastric and colorectal carcinoma, immunohistochemical detection of p53 protein in routinely fixed tissue can be used along with other established parameters to assess prognostic outcome, especially to identify patients with poor short-term prognosis.

Full text

PDF
559

Images in this article

560Figure 1
on p.560

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arai N., Nomura D., Yokota K., Wolf D., Brill E., Shohat O., Rotter V. Immunologically distinct p53 molecules generated by alternative splicing. Mol Cell Biol. 1986 Sep;6(9):3232–3239. doi: 10.1128/mcb.6.9.3232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baker S. J., Fearon E. R., Nigro J. M., Hamilton S. R., Preisinger A. C., Jessup J. M., vanTuinen P., Ledbetter D. H., Barker D. F., Nakamura Y. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science. 1989 Apr 14;244(4901):217–221. doi: 10.1126/science.2649981. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Bártek J., Bártková J., Vojtesek B., Stasková Z., Rejthar A., Kovarík J., Lane D. P. Patterns of expression of the p53 tumour suppressor in human breast tissues and tumours in situ and in vitro. Int J Cancer. 1990 Nov 15;46(5):839–844. doi: 10.1002/ijc.2910460515. [DOI] [PubMed] [Google Scholar]
  5. Bártková J., Bártek J., Lukás J., Vojtesek B., Stasková Z., Rejthar A., Kovarík J., Midgley C. A., Lane D. P. p53 protein alterations in human testicular cancer including pre-invasive intratubular germ-cell neoplasia. Int J Cancer. 1991 Sep 9;49(2):196–202. doi: 10.1002/ijc.2910490209. [DOI] [PubMed] [Google Scholar]
  6. Campo E., de la Calle-Martin O., Miquel R., Palacin A., Romero M., Fabregat V., Vives J., Cardesa A., Yague J. Loss of heterozygosity of p53 gene and p53 protein expression in human colorectal carcinomas. Cancer Res. 1991 Aug 15;51(16):4436–4442. [PubMed] [Google Scholar]
  7. 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]
  8. Chen P. L., Chen Y. M., Bookstein R., Lee W. H. Genetic mechanisms of tumor suppression by the human p53 gene. Science. 1990 Dec 14;250(4987):1576–1580. doi: 10.1126/science.2274789. [DOI] [PubMed] [Google Scholar]
  9. Crawford L. V., Pim D. C., Lamb P. The cellular protein p53 in human tumours. Mol Biol Med. 1984 Aug;2(4):261–272. [PubMed] [Google Scholar]
  10. Davidoff A. M., Herndon J. E., 2nd, Glover N. S., Kerns B. J., Pence J. C., Iglehart J. D., Marks J. R. Relation between p53 overexpression and established prognostic factors in breast cancer. Surgery. 1991 Aug;110(2):259–264. [PubMed] [Google Scholar]
  11. Davidoff A. M., Kerns B. J., Iglehart J. D., Marks J. R. Maintenance of p53 alterations throughout breast cancer progression. Cancer Res. 1991 May 15;51(10):2605–2610. [PubMed] [Google Scholar]
  12. Diller L., Kassel J., Nelson C. E., Gryka M. A., Litwak G., Gebhardt M., Bressac B., Ozturk M., Baker S. J., Vogelstein B. p53 functions as a cell cycle control protein in osteosarcomas. Mol Cell Biol. 1990 Nov;10(11):5772–5781. doi: 10.1128/mcb.10.11.5772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Gannon J. V., Greaves R., Iggo R., Lane D. P. Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form. EMBO J. 1990 May;9(5):1595–1602. doi: 10.1002/j.1460-2075.1990.tb08279.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Isaacs W. B., Carter B. S., Ewing C. M. Wild-type p53 suppresses growth of human prostate cancer cells containing mutant p53 alleles. Cancer Res. 1991 Sep 1;51(17):4716–4720. [PubMed] [Google Scholar]
  18. 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]
  19. Nigro J. M., Baker S. J., Preisinger A. C., Jessup J. M., Hostetter R., Cleary K., Bigner S. H., Davidson N., Baylin S., Devilee P. Mutations in the p53 gene occur in diverse human tumour types. Nature. 1989 Dec 7;342(6250):705–708. doi: 10.1038/342705a0. [DOI] [PubMed] [Google Scholar]
  20. Oren M., Maltzman W., Levine A. J. Post-translational regulation of the 54K cellular tumor antigen in normal and transformed cells. Mol Cell Biol. 1981 Feb;1(2):101–110. doi: 10.1128/mcb.1.2.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Remvikos Y., Laurent-Puig P., Salmon R. J., Frelat G., Dutrillaux B., Thomas G. Simultaneous monitoring of P53 protein and DNA content of colorectal adenocarcinomas by flow cytometry. Int J Cancer. 1990 Mar 15;45(3):450–456. doi: 10.1002/ijc.2910450313. [DOI] [PubMed] [Google Scholar]
  22. Rodrigues N. R., Rowan A., Smith M. E., Kerr I. B., Bodmer W. F., Gannon J. V., Lane D. P. p53 mutations in colorectal cancer. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7555–7559. doi: 10.1073/pnas.87.19.7555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Takahashi T., Nau M. M., Chiba I., Birrer M. J., Rosenberg R. K., Vinocour M., Levitt M., Pass H., Gazdar A. F., Minna J. D. p53: a frequent target for genetic abnormalities in lung cancer. Science. 1989 Oct 27;246(4929):491–494. doi: 10.1126/science.2554494. [DOI] [PubMed] [Google Scholar]
  25. Tamura G., Kihana T., Nomura K., Terada M., Sugimura T., Hirohashi S. Detection of frequent p53 gene mutations in primary gastric cancer by cell sorting and polymerase chain reaction single-strand conformation polymorphism analysis. Cancer Res. 1991 Jun 1;51(11):3056–3058. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES