Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1990 Jul;137(1):103–111.

HER-2/neu oncogene expression and proliferation in breast cancers.

S S Bacus 1, S G Ruby 1, D S Weinberg 1, D Chin 1, R Ortiz 1, J W Bacus 1
PMCID: PMC1877709  PMID: 1973597

Abstract

Amplification of the HER-2/neu proto-oncogene in breast cancer has been reported to correlate with poor patient prognosis. The proliferation, or growth fraction, of cells has also been shown to be of prognostic importance in breast cancer. A study was conducted to evaluate the correlation between HER-2/neu gene expression and proliferation in breast cancer. Quantitative immunohistochemical methods for the detection of the HER-2/neu protein expression and for assessing the proliferation fraction on frozen sections of tumor cells were used. The detection of epidermal growth factor receptor (EGFR) along with quantitative DNA ploidy analysis, also was performed on the same breast cancers. The results indicated two subgroups of invasive ductal carcinoma; 1) HER-2/neu overexpressing cases that were negative for EGFR expression and had low proliferation fraction, and a tetraploid DNA pattern (22 cases), and 2) other combinations of HER-2/neu expression and EGFR expression, with a high proliferation fraction and an aneuploid DNA pattern (38 cases). Eight cases of carcinoma in situ were positive for HER-2/neu overexpression and negative for EGFR expression, and had a high proliferation fraction and a tetraploid DNA pattern. Twenty-six cases of low-grade carcinoma exhibited low proliferation and a diploid DNA pattern.

Full text

PDF
105

Images in this article

Selected References

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

  1. Auer G., Eriksson E., Azavedo E., Caspersson T., Wallgren A. Prognostic significance of nuclear DNA content in mammary adenocarcinomas in humans. Cancer Res. 1984 Jan;44(1):394–396. [PubMed] [Google Scholar]
  2. Bacus S. S., Bacus J. W., Slamon D. J., Press M. F. HER-2/neu oncogene expression and DNA ploidy analysis in breast cancer. Arch Pathol Lab Med. 1990 Feb;114(2):164–169. [PubMed] [Google Scholar]
  3. Bacus S. S., Goldschmidt R., Chin D., Moran G., Weinberg D., Bacus J. W. Biological grading of breast cancer using antibodies to proliferating cells and other markers. Am J Pathol. 1989 Nov;135(5):783–792. [PMC free article] [PubMed] [Google Scholar]
  4. Bacus S., Flowers J. L., Press M. F., Bacus J. W., McCarty K. S., Jr The evaluation of estrogen receptor in primary breast carcinoma by computer-assisted image analysis. Am J Clin Pathol. 1988 Sep;90(3):233–239. doi: 10.1093/ajcp/90.3.233. [DOI] [PubMed] [Google Scholar]
  5. Bouzubar N., Walker K. J., Griffiths K., Ellis I. O., Elston C. W., Robertson J. F., Blamey R. W., Nicholson R. I. Ki67 immunostaining in primary breast cancer: pathological and clinical associations. Br J Cancer. 1989 Jun;59(6):943–947. doi: 10.1038/bjc.1989.200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Clark G. M., Dressler L. G., Owens M. A., Pounds G., Oldaker T., McGuire W. L. Prediction of relapse or survival in patients with node-negative breast cancer by DNA flow cytometry. N Engl J Med. 1989 Mar 9;320(10):627–633. doi: 10.1056/NEJM198903093201003. [DOI] [PubMed] [Google Scholar]
  7. Cornelisse C. J., van de Velde C. J., Caspers R. J., Moolenaar A. J., Hermans J. DNA ploidy and survival in breast cancer patients. Cytometry. 1987 Mar;8(2):225–234. doi: 10.1002/cyto.990080217. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Fallenius A. G., Auer G. U., Carstensen J. M. Prognostic significance of DNA measurements in 409 consecutive breast cancer patients. Cancer. 1988 Jul 15;62(2):331–341. doi: 10.1002/1097-0142(19880715)62:2<331::aid-cncr2820620218>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  10. Gerdes J., Lelle R. J., Pickartz H., Heidenreich W., Schwarting R., Kurtsiefer L., Stauch G., Stein H. Growth fractions in breast cancers determined in situ with monoclonal antibody Ki-67. J Clin Pathol. 1986 Sep;39(9):977–980. doi: 10.1136/jcp.39.9.977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gerdes J., Schwab U., Lemke H., Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer. 1983 Jan 15;31(1):13–20. doi: 10.1002/ijc.2910310104. [DOI] [PubMed] [Google Scholar]
  12. Hudziak R. M., Lewis G. D., Shalaby M. R., Eessalu T. E., Aggarwal B. B., Ullrich A., Shepard H. M. Amplified expression of the HER2/ERBB2 oncogene induces resistance to tumor necrosis factor alpha in NIH 3T3 cells. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5102–5106. doi: 10.1073/pnas.85.14.5102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. McDivitt R. W., Stone K. R., Craig R. B., Meyer J. S. A comparison of human breast cancer cell kinetics measured by flow cytometry and thymidine labeling. Lab Invest. 1985 Mar;52(3):287–291. [PubMed] [Google Scholar]
  15. Meyer J. S., Coplin M. D. Thymidine labeling index, flow cytometric S-phase measurement, and DNA index in human tumors. Comparisons and correlations. Am J Clin Pathol. 1988 May;89(5):586–595. doi: 10.1093/ajcp/89.5.586. [DOI] [PubMed] [Google Scholar]
  16. Sainsbury J. R., Farndon J. R., Harris A. L., Sherbet G. V. Epidermal growth factor receptors on human breast cancers. Br J Surg. 1985 Mar;72(3):186–188. doi: 10.1002/bjs.1800720309. [DOI] [PubMed] [Google Scholar]
  17. Schechter A. L., Stern D. F., Vaidyanathan L., Decker S. J., Drebin J. A., Greene M. I., Weinberg R. A. The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature. 1984 Dec 6;312(5994):513–516. doi: 10.1038/312513a0. [DOI] [PubMed] [Google Scholar]
  18. Schwartz B. R., Pinkus G., Bacus S., Toder M., Weinberg D. S. Cell proliferation in non-Hodgkin's lymphomas. Digital image analysis of Ki-67 antibody staining. Am J Pathol. 1989 Feb;134(2):327–336. [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Taylor S. R., Titus-Ernstoff L., Stitely S. Central values and variation of measured nuclear DNA content in imprints of normal tissues determined by image analysis. Cytometry. 1989 Jul;10(4):382–387. doi: 10.1002/cyto.990100404. [DOI] [PubMed] [Google Scholar]
  22. Waterfield M. D., Mayes E. L., Stroobant P., Bennet P. L., Young S., Goodfellow P. N., Banting G. S., Ozanne B. A monoclonal antibody to the human epidermal growth factor receptor. J Cell Biochem. 1982;20(2):149–161. doi: 10.1002/jcb.240200207. [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. 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]
  25. 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]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES