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British Journal of Cancer logoLink to British Journal of Cancer
. 1990 Jan;61(1):39–45. doi: 10.1038/bjc.1990.9

C-erbB2 mRNA expression in human breast tumours: comparison with c-erbB2 DNA amplification and correlation with prognosis.

H C Parkes 1, K Lillycrop 1, A Howell 1, R K Craig 1
PMCID: PMC1971341  PMID: 2153396

Abstract

In this study, we have investigated the expression of the proto-oncogene c-erbB2 in a total of 70 human primary breast tumours. In agreement with other workers, we observed c-erbB2 gene amplification in 17.5% of the tumours studied. In addition, we carried out a comprehensive analysis of c-erbB2 mRNA expression in the tumours using RNase mapping and in situ hybridisation techniques. Our results indicated a more frequent (30%) overexpression of c-erbB2 mRNA, which was associated only with breast carcinomas of a ductal origin. Furthermore, analysis of the c-erbB2 mRNA gene locus in the same tumours demonstrated that enhanced c-erbB2 expression could occur in the presence or absence of gene amplification, suggesting that additional molecular mechanisms may result in overexpression of c-erbB2 mRNA in human mammary tumours. In situ hybridisation showed that elevated levels of c-erbB2 mRNA were specific to malignant cells within the breast tumour. Analysis of the association between c-erbB2 mRNA overexpression and clinicopathological factors revealed a significant correlation with poor tumour grade, but not with steroid receptor status or patient menopausal status. No significant correlation was observed between overexpression of c-erbB2 mRNA and early disease recurrence in our group of patients, although there was a definite trend towards poorer prognosis.

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Selected References

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  1. Akiyama T., Sudo C., Ogawara H., Toyoshima K., Yamamoto T. The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Science. 1986 Jun 27;232(4758):1644–1646. doi: 10.1126/science.3012781. [DOI] [PubMed] [Google Scholar]
  2. Ali I. U., Campbell G., Lidereau R., Callahan R. Lack of evidence for the prognostic significance of c-erbB-2 amplification in human breast carcinoma. Oncogene Res. 1988 Sep;3(2):139–146. [PubMed] [Google Scholar]
  3. Bargmann C. I., Hung M. C., Weinberg R. A. The neu oncogene encodes an epidermal growth factor receptor-related protein. Nature. 1986 Jan 16;319(6050):226–230. doi: 10.1038/319226a0. [DOI] [PubMed] [Google Scholar]
  4. Barnes D. M., Lammie G. A., Millis R. R., Gullick W. L., Allen D. S., Altman D. G. An immunohistochemical evaluation of c-erbB-2 expression in human breast carcinoma. Br J Cancer. 1988 Oct;58(4):448–452. doi: 10.1038/bjc.1988.238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berger M. S., Locher G. W., Saurer S., Gullick W. J., Waterfield M. D., Groner B., Hynes N. E. Correlation of c-erbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading. Cancer Res. 1988 Mar 1;48(5):1238–1243. [PubMed] [Google Scholar]
  6. Boel E., Vuust J., Norris F., Norris K., Wind A., Rehfeld J. F., Marcker K. A. Molecular cloning of human gastrin cDNA: evidence for evolution of gastrin by gene duplication. Proc Natl Acad Sci U S A. 1983 May;80(10):2866–2869. doi: 10.1073/pnas.80.10.2866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Coussens L., Yang-Feng T. L., Liao Y. C., Chen E., Gray A., McGrath J., Seeburg P. H., Libermann T. A., Schlessinger J., Francke U. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science. 1985 Dec 6;230(4730):1132–1139. doi: 10.1126/science.2999974. [DOI] [PubMed] [Google Scholar]
  8. Di Fiore P. P., Pierce J. H., Kraus M. H., Segatto O., King C. R., Aaronson S. A. erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells. Science. 1987 Jul 10;237(4811):178–182. doi: 10.1126/science.2885917. [DOI] [PubMed] [Google Scholar]
  9. Dietzsch E., Retief A. E., Lotze M. J., Warnich L., Nicholson D. L., Fox M. F., Fricke J., du Plessis L., Oosthuizen C. J. An anonymous human single copy genomic clone, D5S6 (M4) on chromosome 5 identifies a three allele RFLP. Nucleic Acids Res. 1986 Feb 25;14(4):1923–1923. doi: 10.1093/nar/14.4.1923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Escot C., Theillet C., Lidereau R., Spyratos F., Champeme M. H., Gest J., Callahan R. Genetic alteration of the c-myc protooncogene (MYC) in human primary breast carcinomas. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4834–4838. doi: 10.1073/pnas.83.13.4834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  12. Gusterson B. A., Machin L. G., Gullick W. J., Gibbs N. M., Powles T. J., Elliott C., Ashley S., Monaghan P., Harrison S. c-erbB-2 expression in benign and malignant breast disease. Br J Cancer. 1988 Oct;58(4):453–457. doi: 10.1038/bjc.1988.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jeanpierre M. A rapid method for the purification of DNA from blood. Nucleic Acids Res. 1987 Nov 25;15(22):9611–9611. doi: 10.1093/nar/15.22.9611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kraus M. H., Popescu N. C., Amsbaugh S. C., King C. R. Overexpression of the EGF receptor-related proto-oncogene erbB-2 in human mammary tumor cell lines by different molecular mechanisms. EMBO J. 1987 Mar;6(3):605–610. doi: 10.1002/j.1460-2075.1987.tb04797.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Parkes H., Collis P., Baildam A., Ralphs D., Lyons B., Howell A., Craig R. In situ hybridisation and S1 mapping show that the presence of infiltrating plasma cells is associated with poor prognosis in breast cancer. Br J Cancer. 1988 Dec;58(6):715–722. doi: 10.1038/bjc.1988.296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Slamon D. J., Clark G. M. Amplification of c-erbB-2 and aggressive human breast tumors? Science. 1988 Jun 24;240(4860):1795–1798. doi: 10.1126/science.3289120. [DOI] [PubMed] [Google Scholar]
  17. Slamon D. J., Clark G. M. In Reply: Amplification c-erbB-2 and Aggressive Human Breast Tumors? Science. 1988 Jun 24;240(4860):1796–1798. doi: 10.1126/science.240.4860.1796. [DOI] [PubMed] [Google Scholar]
  18. Slamon D. J., Clark G. M., Wong S. G., Levin W. J., Ullrich A., McGuire W. L. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987 Jan 9;235(4785):177–182. doi: 10.1126/science.3798106. [DOI] [PubMed] [Google Scholar]
  19. Smith R., Peters G., Dickson C. Multiple RNAs expressed from the int-2 gene in mouse embryonal carcinoma cell lines encode a protein with homology to fibroblast growth factors. EMBO J. 1988 Apr;7(4):1013–1022. doi: 10.1002/j.1460-2075.1988.tb02908.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Varley J. M., Swallow J. E., Brammar W. J., Whittaker J. L., Walker R. A. Alterations to either c-erbB-2(neu) or c-myc proto-oncogenes in breast carcinomas correlate with poor short-term prognosis. Oncogene. 1987;1(4):423–430. [PubMed] [Google Scholar]
  21. 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]
  22. Whittaker J. L., Walker R. A., Varley J. M. Differential expression of cellular oncogenes in benign and malignant human breast tissue. Int J Cancer. 1986 Nov 15;38(5):651–655. doi: 10.1002/ijc.2910380506. [DOI] [PubMed] [Google Scholar]
  23. Wright C., Angus B., Nicholson S., Sainsbury J. R., Cairns J., Gullick W. J., Kelly P., Harris A. L., Horne C. H. Expression of c-erbB-2 oncoprotein: a prognostic indicator in human breast cancer. Cancer Res. 1989 Apr 15;49(8):2087–2090. [PubMed] [Google Scholar]
  24. Yamamoto T., Ikawa S., Akiyama T., Semba K., Nomura N., Miyajima N., Saito T., Toyoshima K. Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor. Nature. 1986 Jan 16;319(6050):230–234. doi: 10.1038/319230a0. [DOI] [PubMed] [Google Scholar]
  25. Yokota J., Yamamoto T., Toyoshima K., Terada M., Sugimura T., Battifora H., Cline M. J. Amplification of c-erbB-2 oncogene in human adenocarcinomas in vivo. Lancet. 1986 Apr 5;1(8484):765–767. doi: 10.1016/s0140-6736(86)91782-4. [DOI] [PubMed] [Google Scholar]
  26. Zeillinger R., Kury F., Czerwenka K., Kubista E., Sliutz G., Knogler W., Huber J., Zielinski C., Reiner G., Jakesz R. HER-2 amplification, steroid receptors and epidermal growth factor receptor in primary breast cancer. Oncogene. 1989 Jan;4(1):109–114. [PubMed] [Google Scholar]
  27. Zhou D. J., Ahuja H., Cline M. J. Proto-oncogene abnormalities in human breast cancer: c-ERBB-2 amplification does not correlate with recurrence of disease. Oncogene. 1989 Jan;4(1):105–108. [PubMed] [Google Scholar]
  28. Zhou D., Battifora H., Yokota J., Yamamoto T., Cline M. J. Association of multiple copies of the c-erbB-2 oncogene with spread of breast cancer. Cancer Res. 1987 Nov 15;47(22):6123–6125. [PubMed] [Google Scholar]
  29. Zinn K., DiMaio D., Maniatis T. Identification of two distinct regulatory regions adjacent to the human beta-interferon gene. Cell. 1983 Oct;34(3):865–879. doi: 10.1016/0092-8674(83)90544-5. [DOI] [PubMed] [Google Scholar]
  30. van de Vijver M. J., Peterse J. L., Mooi W. J., Wisman P., Lomans J., Dalesio O., Nusse R. Neu-protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer. N Engl J Med. 1988 Nov 10;319(19):1239–1245. doi: 10.1056/NEJM198811103191902. [DOI] [PubMed] [Google Scholar]
  31. van de Vijver M., van de Bersselaar R., Devilee P., Cornelisse C., Peterse J., Nusse R. Amplification of the neu (c-erbB-2) oncogene in human mammmary tumors is relatively frequent and is often accompanied by amplification of the linked c-erbA oncogene. Mol Cell Biol. 1987 May;7(5):2019–2023. doi: 10.1128/mcb.7.5.2019. [DOI] [PMC free article] [PubMed] [Google Scholar]

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