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. 1992 Sep;66(3):583–588. doi: 10.1038/bjc.1992.318

p53 protein expression in human breast carcinoma: relationship to expression of epidermal growth factor receptor, c-erbB-2 protein overexpression, and oestrogen receptor.

D N Poller 1, C E Hutchings 1, M Galea 1, J A Bell 1, R A Nicholson 1, C W Elston 1, R W Blamey 1, I O Ellis 1
PMCID: PMC1977948  PMID: 1355662

Abstract

The expression of p53 protein, oestrogen receptor protein, epidermal growth factor receptor (EGFR) and overexpression of the c-erbB-2 oncoprotein was examined in a series of 149 primary symptomatic breast carcinomas. Expression of p53 was present in 62 of 146 cases (42.5%) of the invasive carcinoma and one of three cases (33.3%) of ductal carcinoma in situ (DCIS) examined. Statistical associations of tumour oestrogen receptor positivity and lack of p53 protein expression, chi 2 = 19.78 (d.f. = 1), P less than 0.001, positive tumour p53 status and poor tumour grade; chi 2 = 14.1 (d.f. = 2), P less than 0.001, EGFR expression chi 2 = 7.07, (d.f. = 1), P less than 0.01 and tumour c-erbB-2 protein overexpression; chi 2 = 4.61 (d.f. = 1), P = 0.032 were identified. Expression of p53 is rare in invasive lobular carcinoma of classical type (8.3% of cases examined) in contrast to other common types of mammary carcinoma. Non-significant trends of p53 protein expression and increased regional tumour recurrence; chi 2 = 3.20 (d.f. = 1), P = 0.074 and also poorer patient survival; chi 2 = 3.76 (d.f. = 1), P = 0.053 were identified. p53 protein expression is a common event in human breast cancer and is present in both DCIS and invasive mammary carcinoma. Abnormal expression of p53 protein is a feature of both in situ and invasive breast carcinoma, implying that the abnormal p53 protein expression may be implicated in the early stages of mammary carcinoma progression.

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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. 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]
  3. 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]
  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. Casey G., Lo-Hsueh M., Lopez M. E., Vogelstein B., Stanbridge E. J. Growth suppression of human breast cancer cells by the introduction of a wild-type p53 gene. Oncogene. 1991 Oct;6(10):1791–1797. [PubMed] [Google Scholar]
  6. Cattoretti G., Andreola S., Clemente C., D'Amato L., Rilke F. Vimentin and p53 expression on epidermal growth factor receptor-positive, oestrogen receptor-negative breast carcinomas. Br J Cancer. 1988 Apr;57(4):353–357. doi: 10.1038/bjc.1988.81. [DOI] [PMC free article] [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. Dang C. V., Lee W. M. Nuclear and nucleolar targeting sequences of c-erb-A, c-myb, N-myc, p53, HSP70, and HIV tat proteins. J Biol Chem. 1989 Oct 25;264(30):18019–18023. [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Donehower L. A., Harvey M., Slagle B. L., McArthur M. J., Montgomery C. A., Jr, Butel J. S., Bradley A. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature. 1992 Mar 19;356(6366):215–221. doi: 10.1038/356215a0. [DOI] [PubMed] [Google Scholar]
  12. Ellis I. O., Galea M., Broughton N., Locker A., Blamey R. W., Elston C. W. Pathological prognostic factors in breast cancer. II. Histological type. Relationship with survival in a large study with long-term follow-up. Histopathology. 1992 Jun;20(6):479–489. doi: 10.1111/j.1365-2559.1992.tb01032.x. [DOI] [PubMed] [Google Scholar]
  13. Elston C. W., Ellis I. O. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991 Nov;19(5):403–410. doi: 10.1111/j.1365-2559.1991.tb00229.x. [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. Harris A. L. Cancer genes. Telling changes of base. Nature. 1991 Apr 4;350(6317):377–378. doi: 10.1038/350377a0. [DOI] [PubMed] [Google Scholar]
  16. Hollstein M., Sidransky D., Vogelstein B., Harris C. C. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. doi: 10.1126/science.1905840. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. 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]
  20. 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]
  21. Linzer D. I., Levine A. J. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell. 1979 May;17(1):43–52. doi: 10.1016/0092-8674(79)90293-9. [DOI] [PubMed] [Google Scholar]
  22. Lovekin C., Ellis I. O., Locker A., Robertson J. F., Bell J., Nicholson R., Gullick W. J., Elston C. W., Blamey R. W. c-erbB-2 oncoprotein expression in primary and advanced breast cancer. Br J Cancer. 1991 Mar;63(3):439–443. doi: 10.1038/bjc.1991.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mackay J., Steel C. M., Elder P. A., Forrest A. P., Evans H. J. Allele loss on short arm of chromosome 17 in breast cancers. Lancet. 1988 Dec 17;2(8625):1384–1385. doi: 10.1016/s0140-6736(88)90584-3. [DOI] [PubMed] [Google Scholar]
  24. Melero J. A., Tur S., Carroll R. B. Host nuclear proteins expressed in simian virus 40-transformed and -infected cells. Proc Natl Acad Sci U S A. 1980 Jan;77(1):97–101. doi: 10.1073/pnas.77.1.97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Milner J. The role of p53 in the normal control of cell proliferation. Curr Opin Cell Biol. 1991 Apr;3(2):282–286. doi: 10.1016/0955-0674(91)90153-p. [DOI] [PubMed] [Google Scholar]
  26. Milner J., Watson J. V. Addition of fresh medium induces cell cycle and conformation changes in p53, a tumour suppressor protein. Oncogene. 1990 Nov;5(11):1683–1690. [PubMed] [Google Scholar]
  27. Nowell P. C. The clonal evolution of tumor cell populations. Science. 1976 Oct 1;194(4260):23–28. doi: 10.1126/science.959840. [DOI] [PubMed] [Google Scholar]
  28. Ostrowski J. L., Sawan A., Henry L., Wright C., Henry J. A., Hennessy C., Lennard T. J., Angus B., Horne C. H. p53 expression in human breast cancer related to survival and prognostic factors: an immunohistochemical study. J Pathol. 1991 May;164(1):75–81. doi: 10.1002/path.1711640113. [DOI] [PubMed] [Google Scholar]
  29. Prosser J., Thompson A. M., Cranston G., Evans H. J. Evidence that p53 behaves as a tumour suppressor gene in sporadic breast tumours. Oncogene. 1990 Oct;5(10):1573–1579. [PubMed] [Google Scholar]
  30. Raycroft L., Wu H. Y., Lozano G. Transcriptional activation by wild-type but not transforming mutants of the p53 anti-oncogene. Science. 1990 Aug 31;249(4972):1049–1051. doi: 10.1126/science.2144364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sainsbury J. R., Farndon J. R., Needham G. K., Malcolm A. J., Harris A. L. Epidermal-growth-factor receptor status as predictor of early recurrence of and death from breast cancer. Lancet. 1987 Jun 20;1(8547):1398–1402. doi: 10.1016/s0140-6736(87)90593-9. [DOI] [PubMed] [Google Scholar]
  32. Sidransky D., Mikkelsen T., Schwechheimer K., Rosenblum M. L., Cavanee W., Vogelstein B. Clonal expansion of p53 mutant cells is associated with brain tumour progression. Nature. 1992 Feb 27;355(6363):846–847. doi: 10.1038/355846a0. [DOI] [PubMed] [Google Scholar]
  33. Slamon D. J., Godolphin W., Jones L. A., Holt J. A., Wong S. G., Keith D. E., Levin W. J., Stuart S. G., Udove J., Ullrich A. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989 May 12;244(4905):707–712. doi: 10.1126/science.2470152. [DOI] [PubMed] [Google Scholar]
  34. Thompson A. M., Steel C. M., Chetty U., Hawkins R. A., Miller W. R., Carter D. C., Forrest A. P., Evans H. J. p53 gene mRNA expression and chromosome 17p allele loss in breast cancer. Br J Cancer. 1990 Jan;61(1):74–78. doi: 10.1038/bjc.1990.17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Todd J. H., Dowle C., Williams M. R., Elston C. W., Ellis I. O., Hinton C. P., Blamey R. W., Haybittle J. L. Confirmation of a prognostic index in primary breast cancer. Br J Cancer. 1987 Oct;56(4):489–492. doi: 10.1038/bjc.1987.230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Venter D. J., Tuzi N. L., Kumar S., Gullick W. J. Overexpression of the c-erbB-2 oncoprotein in human breast carcinomas: immunohistological assessment correlates with gene amplification. Lancet. 1987 Jul 11;2(8550):69–72. doi: 10.1016/s0140-6736(87)92736-x. [DOI] [PubMed] [Google Scholar]
  37. Walker R. A., Dearing S. J., Lane D. P., Varley J. M. Expression of p53 protein in infiltrating and in-situ breast carcinomas. J Pathol. 1991 Nov;165(3):203–211. doi: 10.1002/path.1711650303. [DOI] [PubMed] [Google Scholar]
  38. Wynford-Thomas D. P53 in tumour pathology: can we trust immunocytochemistry? J Pathol. 1992 Apr;166(4):329–330. doi: 10.1002/path.1711660402. [DOI] [PubMed] [Google Scholar]

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