Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1996 Jul;74(2):229–233. doi: 10.1038/bjc.1996.342

C-erbB-3 in human breast carcinoma: expression and relation to prognosis and established prognostic indicators.

A Travis 1, S E Pinder 1, J F Robertson 1, J A Bell 1, P Wencyk 1, W J Gullick 1, R I Nicholson 1, D N Poller 1, R W Blamey 1, C W Elston 1, I O Ellis 1
PMCID: PMC2074568  PMID: 8688326

Abstract

A series of 346 patients with primary operable breast cancer and a series of 145 patients with advanced breast cancer were investigated for c-erbB-3 protein expression using the monoclonal antibody RTJ1. Formalin-fixed, paraffin-embedded tumour samples were stained using a standard immunochemical method and staining was assessed on a four-point scale. The study aimed to observe the expression of the c-erbB-3 protein and investigate any relationship between expression and established prognostic indicators and prognosis. In both the primary and advanced series breast tumour tissue was found to stain heterogeneously for c-erbB-3. The staining was observed to be predominantly cytoplasmic and the majority of tumours exhibited moderate positivity. However, 15% and 35% of cases in the primary operable and advanced series respectively displayed strong positive staining. No significant difference was found between the staining in the primary and advanced series. In the primary operable breast cancers, no significant associations were demonstrated with overall survival, disease-free interval, regional recurrence, the presence of distant metastases, age, menopausal status, oestrogen receptor status, histological grade, lymph node stage, vascular invasion and c-erbB-2 protein expression. However, a significant association was seen between the degree of c-erbB-3 immunoreactivity and both tumour size (P < 0.01) and tumour type prognostic group (P = 0.05). No overall association with local recurrence was seen when the four groups of c-erbB-3 expression were analysed (P = 0.12), but when those tumours showing no or weak staining were compared with those showing moderate and strong immunoreactivity it was seen that the latter were significantly more likely to develop local recurrence (P = 0.03). In the series of patients with advanced disease, no significant associations were demonstrated with survival, UICC criteria, age, menopausal status, oestrogen receptor status, histological grade, c-erbB-2 status or the presence of vascular invasion. In conclusion this study found variable expression of c-erbB-3 protein in human breast carcinoma and an association with some recognised prognostic factors in those patients with primary operable breast carcinoma. It seems, however, unlikely that c-erbB-3 protein expression will emerge as a powerful enough prognostic factor to be of value in clinical practice.

Full text

PDF
229

Images in this article

Selected References

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

  1. Carraway K. L., 3rd, Sliwkowski M. X., Akita R., Platko J. V., Guy P. M., Nuijens A., Diamonti A. J., Vandlen R. L., Cantley L. C., Cerione R. A. The erbB3 gene product is a receptor for heregulin. J Biol Chem. 1994 May 13;269(19):14303–14306. [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Grimaux M., Romain S., Remvikos Y., Martin P. M., Magdelénat H. Prognostic value of epidermal growth factor receptor in node-positive breast cancer. Breast Cancer Res Treat. 1989 Oct;14(1):77–90. doi: 10.1007/BF01805978. [DOI] [PubMed] [Google Scholar]
  5. Gullick W. J., Love S. B., Wright C., Barnes D. M., Gusterson B., Harris A. L., Altman D. G. c-erbB-2 protein overexpression in breast cancer is a risk factor in patients with involved and uninvolved lymph nodes. Br J Cancer. 1991 Mar;63(3):434–438. doi: 10.1038/bjc.1991.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Haybittle J. L., Blamey R. W., Elston C. W., Johnson J., Doyle P. J., Campbell F. C., Nicholson R. I., Griffiths K. A prognostic index in primary breast cancer. Br J Cancer. 1982 Mar;45(3):361–366. doi: 10.1038/bjc.1982.62. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kraus M. H., Fedi P., Starks V., Muraro R., Aaronson S. A. Demonstration of ligand-dependent signaling by the erbB-3 tyrosine kinase and its constitutive activation in human breast tumor cells. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2900–2904. doi: 10.1073/pnas.90.7.2900. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lemoine N. R., Barnes D. M., Hollywood D. P., Hughes C. M., Smith P., Dublin E., Prigent S. A., Gullick W. J., Hurst H. C. Expression of the ERBB3 gene product in breast cancer. Br J Cancer. 1992 Dec;66(6):1116–1121. doi: 10.1038/bjc.1992.420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Nicholson S., Wright C., Sainsbury J. R., Halcrow P., Kelly P., Angus B., Farndon J. R., Harris A. L. Epidermal growth factor receptor (EGFr) as a marker for poor prognosis in node-negative breast cancer patients: neu and tamoxifen failure. J Steroid Biochem Mol Biol. 1990 Dec 20;37(6):811–814. doi: 10.1016/0960-0760(90)90424-j. [DOI] [PubMed] [Google Scholar]
  11. Pereira H., Pinder S. E., Sibbering D. M., Galea M. H., Elston C. W., Blamey R. W., Robertson J. F., Ellis I. O. Pathological prognostic factors in breast cancer. IV: Should you be a typer or a grader? A comparative study of two histological prognostic features in operable breast carcinoma. Histopathology. 1995 Sep;27(3):219–226. doi: 10.1111/j.1365-2559.1995.tb00213.x. [DOI] [PubMed] [Google Scholar]
  12. Pinder S. E., Ellis I. O., Galea M., O'Rouke S., Blamey R. W., Elston C. W. Pathological prognostic factors in breast cancer. III. Vascular invasion: relationship with recurrence and survival in a large study with long-term follow-up. Histopathology. 1994 Jan;24(1):41–47. doi: 10.1111/j.1365-2559.1994.tb01269.x. [DOI] [PubMed] [Google Scholar]
  13. Plowman G. D., Green J. M., Culouscou J. M., Carlton G. W., Rothwell V. M., Buckley S. Heregulin induces tyrosine phosphorylation of HER4/p180erbB4. Nature. 1993 Dec 2;366(6454):473–475. doi: 10.1038/366473a0. [DOI] [PubMed] [Google Scholar]
  14. Poller D. N., Spendlove I., Baker C., Church R., Ellis I. O., Plowman G. D., Mayer R. J. Production and characterization of a polyclonal antibody to the c-erbB-3 protein: examination of c-erbB-3 protein expression in adenocarcinomas. J Pathol. 1992 Nov;168(3):275–280. doi: 10.1002/path.1711680306. [DOI] [PubMed] [Google Scholar]
  15. Prigent S. A., Lemoine N. R., Hughes C. M., Plowman G. D., Selden C., Gullick W. J. Expression of the c-erbB-3 protein in normal human adult and fetal tissues. Oncogene. 1992 Jul;7(7):1273–1278. [PubMed] [Google Scholar]
  16. Rajkumar T., Gooden C. S., Lemoine N. R., Gullick W. J., Goden C. S. Expression of the c-erbB-3 protein in gastrointestinal tract tumours determined by monoclonal antibody RTJ1. J Pathol. 1993 Jul;170(3):271–278. doi: 10.1002/path.1711700309. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Sainsbury J. R., Malcolm A. J., Appleton D. R., Farndon J. R., Harris A. L. Presence of epidermal growth factor receptor as an indicator of poor prognosis in patients with breast cancer. J Clin Pathol. 1985 Nov;38(11):1225–1228. doi: 10.1136/jcp.38.11.1225. [DOI] [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. Sliwkowski M. X., Schaefer G., Akita R. W., Lofgren J. A., Fitzpatrick V. D., Nuijens A., Fendly B. M., Cerione R. A., Vandlen R. L., Carraway K. L., 3rd Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor for heregulin. J Biol Chem. 1994 May 20;269(20):14661–14665. [PubMed] [Google Scholar]
  21. Walker R. A., Gullick W. J., Varley J. M. An evaluation of immunoreactivity for c-erbB-2 protein as a marker of poor short-term prognosis in breast cancer. Br J Cancer. 1989 Sep;60(3):426–429. doi: 10.1038/bjc.1989.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]

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

RESOURCES