Abstract
In order to assess the specificity of biotinylated anti-c-erbB-3 antibody, screening was performed on a series of tumour cell lines and lymphocytes. Staining was found to be consistent, with good reproducibility. Twenty-nine consecutive breast cancer samples were obtained from women treated with tamoxifen and undergoing elective mastectomy. Twenty-eight invasive ductal carcinomas and 1 DCIS were stained for c-erbB-3 expression: 2 were grade I (Bloom and Richardson), 15 grade II, and 11 grade III tumours, 1 being unclassified; 16 were axillary node positive and 10 node negative; in 2 cases no nodes were sampled. Tumours examined by flow cytometry were stained with cytokeratin FITC antibody and the cytokeratin-positive population gated. Using Mann-Whitney analysis no association was seen between c-erbB-3 expression and Bloom and Richardson grade or axillary node status. In the tumour samples c-erbB-3 expression was found to show an association with EGF-R (P=0.021r 2=0.16), PgR (P=0.02,r 2=0.16), c-myc (P<0.0001,r 2=0.5), c-jun (P=0.001,r 2=0.4) and c-fos (P=0.001,r 2=0.5) but not with c-erbB-2 (P=0.2,r 2=0.06), ER (P=0.4,r 2=0.02) or p53 1801 (P=0.05,r 2=0.2). Expression of c-erbB-3 may not be an independent marker of prognosis, but it is associated with other markers of poor prognosis and early cellular events linked with aberrant growth and differentiation.
Similar content being viewed by others
References
Alkhalaf M, Murphy LJ, Murphy LC (1993) Enhanced c-jun activity alters responsiveness to medroxyprogesterone acetate in Ishikawa human endometrial carcinoma cells. Mol Endocrinol 7: 1634
Bloom HJG, Richardson WW (1957) Histological grading and prognosis in breast cancer. A study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer 11: 259
Brotherick I, Lennard TWJ, Wilkinson SE, Cook S, Angus B, Shenton BK (1994) Flow cytometric method for the measurement of epidermal growth factor receptor and comparison with the radio-ligand binding assay. Cytometry 16: 262
Brotherick I, Lennard TWJ, Cook S, Johnstone R, Angus B, Winthereik MP, Shenton BK (1995) Use of the biotinylated antibody DAKO-ER 1D5 to measure oestrogen receptor on cytokeratin positive cells obtained from primary breast cancer cells. Cytometry 20: 74
Brotherick I, Shenton BK, Lennard TWJ (1995) Are fine needle breast aspirates representative of the underlying solid tumour? A comparison of receptor levels, ploidy and the influence of cytokeratin gates. Br J Cancer 72 732
Berger MS, Locher GW, Saurer S, Gullick WJ, Waterfield MD, Groner B, Hynes NE (1988) Correlation of the c-erbB-2 gene amplifications and protein expression in human breast carcinoma with nodal status and nuclear grading. Cancer Res 48: 1238
Dickson RB, Salomon DS, Lippman ME (1992) Tyrosine kinase receptor: nuclear protooncogene interactions in breast cancer. Cancer Treat Res 61: 249
Elledge RM, Fuqua SA, Clark GM, Pujol P, Allred DC, McGuire WL (1993) Prognostic significance of p53 gene alterations in node-negative breast cancer. Breast Cancer Res Treat 26: 225
Escot C, Theillet C, Lidereau R, Spyratos F (1986) Genetic alterations of the c-myc protooncogene (MYC) in human primary breast carcinomas. Proc Natl Acad Sci USA 83: 4834
Ferrero M, Spyratos F, LeDoussal V, Desplaces A, Rouëssé J (1990) Flow cytometric analysis of DNA content and keratins by using CK7, CK8, CK18, CK19 and KL1 monoclonal antibodies in malignant tumours. Cytometry 11: 716
Fitzpatrick SL, LaChance LP, Schultz GS (1984) Characterization of epidermal growth factor receptor and action on human cancer cells in culture. Cancer Res 44: 3443
Franco S, Jimenez J, Cruz J, Torroella M, Nordenskjold M (1994) High expression of the EGFR in fibroadenomas campared to breast carcinomas. Anticancer Res 14: 1679
Gasparini G, Gullick WJ, Maluta S, Palma PD, Caffo O, Leonardi E, Boracchi P, Pozza F, Lemoine NR, Bevilacqua P (1984) c-erbB-3 and c-erbB-2 protein expression in node negative breast carcinoma — an immunocytochemical study. Eur J Cancer 30A: 16
Howell A, Harland RNL, Bramwell VHC (1984) Steroid-hormone receptors and survival after first relapse in breast cancer. Lancet I: 588
Kraus MH, Issing W, Miki T, Popescu NC, Aaronson SA (1989) Isolation and characterization of erbB-3, a third member of the erbB/epidermal growth factor family; evidence of over-expression in a subset of human mammary tumours. Proc Natl Acad Sci USA 86: 9193
Lane D, Benchimol S (1990) p53: Oncogene or anti-oncogene. Genes Dev 4: 1
Lemoine NR, Barnes DM, Hollywood DP, Hughes CM, Smith P, Dublin E, Prigent SA, Gullick WJ, Hurst HC (1992) Expression of the ERBB3 gene product in breast cancer. Br J Cancer 6: 1116
Lovekin C, Ellis IO, Locker A, Robertson FR, Bell J, Nicholson R, Gullick WJ, Elston CW, Blamey RW (1991) c-erbB-2 oncoprotein expression in primary and advanced breast cancer. Br J Cancer 63: 439
Musgrove EA, Hamilton JA, Lee CS, Sweeney KJ, Watts CK, Sutherland RL (1993) Growth factor, steroid and steroid antagonist regulation of cyclin gene expression associated with changes in T-47D human breast cancer cell cycle progression. Mol Cell Biol 13: 3577
Myers RB, Srivastava S, Oelschlager DK, Grizzle WE (1994) Expression of p160erbB-3 and p185erbB-2 in prostatic intraepithelial neoplasia and prostatic adenocarcinoma. J Natl Cancer Inst 86: 1140
Nagai MA, Marques LA, Yamamoto L, Fujiyama CT, Brentani MM (1994) Estrogen and progesterone receptor mRNA levels in primary breast cancer: association with patient survival and other clinical and tumour features. Int J Cancer 59: 351
Paik S, Hazan R, Fisher ER, Sass RE, Fisher B, Redmond C, Schlessinger J, Lippmann ME, King CR (1990) Pathological findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein overexpression in primary breast cancer. J Clin Oncol 8: 103
Plowman GD, Whitney GS, Neubauer MG (1994) Molecular cloning and expression of an additional epidermal growth factor receptor-related gene. Proc Natl Acad Sci USA 87: 4905
Prigent SA, Lemoine NR (1992) The type 1 (EGF receptor-related) family of growth factor receptors and their ligands. Prog Growth Factor Res 4: 1
Quinn CM, Ostrowski JL, Lane SA, Loney DP, Teasdale J, Benson FA (1994) c-erbB-3 Protein expression in human breast cancer: comparison with other tumour variables and survival. Histopathology 25: 247
Rajkumar T, Gullick WJ (1994) The type I growth factor receptors in human breast cancer. Breast Cancer Res Treat 29: 3
Sainsbury JRC, Farndon JR, Sherbet GV, Harris AL (1985) Epidermal growth factor receptors and oestrogen receptors in human breast cancer. Lancet I: 364
Sainsbury JRC, Malcolm AJ, Appleton DR, Farndon JR, Harris AL (1985) Presence of epidermal growth factor receptor as an indicator of poor prognosis in patients with breast cancer. J Clin Pathol 38: 1225
Sainsbury JRC, Needham GK, Farndon JR, Malcolm AJ, Harris AL (1987) Epidermal growth factor receptor status as a predictor of early recurrence of and death from breast cancer. Lancet I: 1398
Sanidas EE, Filipe MI, Linehan J, Lemoine NR, Gullick WJ, Rajkumar R, Levison DA (1993) Expression of the c-erbB-3 gene product in gastric cancer. Int J Cancer 54: 935
Sawan A, Randall B, Angus B, Wright C, Henry JA, Ostrowski J, Hennessey C, Lennard TWJ, Corbett I, Horne CH (1992) Retinoblastoma and p53 gene expression related to relapse and survival in human breast cancer: an immunohistochemical study. J Pathol (Lond) 168: 23
Slamon DJ, Clark GM, Wong SG, Levin W, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of HER-2/neu proto-oncogene. Science 235: 177
Tavassoli M, Quirke P, Farzaneh F, Lock NJ, Mayne LV, Kirkham N (1989) c-erbB-2/c-erbA co-amplification indicative of lymph node metastasis, andc-myc amplification of high tumour grade, in human breast carcinoma. Br J Cancer 60: 505
Valerius EM, Ciardiello FM, Heldin NE, Blondel B, Merlo G, Smith G, Stampfer MR, Lippman ME, Dickson RB, Salomon DS (1990) Stromal influences on transformation of human epithelial cells over expressing c-myc and SV40T. J Cell Physiol 145: 207
Visscher DV, Zarbo RJ, Green A, Crissman JD (1990) Prognostic significance of morphological parameters and flow cytometric DNA analysis in carcinoma of the breast. Pathol Ann 25: 171
Winstanley J, Cooke T, Murray GD, Platt-Higgins A, George WD, Holt S, Myskov M, Spedding A, Baraclough BR, Rudland PS (1991) The long term prognostic significance of c-erbB-2 in primary breast cancer. Br J Cancer 63: 447
Wosikowski K, Kung W, Hasmann M, Loser R, Eppenberger U (1994) Inhibition of growth factor activated proliferation by antioestrogens and effects on early gene expression of MCF-7 cells. Int J Cancer 53: 290
Wright C, Angus B, Nicholson S, Sainsbury JRC, Cairns J, Gullick WJ, Kelly P, Harris AC, Horne CHW (1989) Expression of c-erbB-2 oncoprotein: a prognostic indicator in human breast cancer. Cancer Res 49: 2087
Author information
Authors and Affiliations
Additional information
This study was supported by The North of England Cancer Research Campaign
Rights and permissions
About this article
Cite this article
Brotherick, I., Shenton, B.K., Angus, B. et al. A flow cytometric study of c-erbB-3 expression in breast cancer. Cancer Immunol Immunother 41, 280–286 (1995). https://doi.org/10.1007/BF01517215
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01517215