Skip to main content
SpringerLink
Log in

Immunohistochemical studies on oncogene products (EGF-R, c-erbB-2) and growth factors (EGF, TGF-α) in human breast cancer: their relationship to oestrogen receptor status, histological grade, mitotic index and nodal status

  • Original Articles
  • Published:
Virchows Archiv A Aims and scope Submit manuscript

Summary

In this investigation, 83 human mammary carcinomas were examined for the expression of oestrogen receptor (ER), epidermal growth factor receptor (EGF-R), epidermal growth factor (EGF), transforming growth factor alpha (TGF-α), c-erbB-2, histological grade, mitotic index and nodal status, all of which are reportedly prognostically significant factors (Bloom and Richardson 1957; Baak et al. 1985; Wright et al. 1989). ER expression was biochemically recognized in 43.4% of mammary carcinomas, and EGF-R, EGF, TGF-α and c-erbB-2 were histochemically recognized in 25.3, 14.5, 27.7 and 18.0% of mammary carcinomas examined respectively, using conventional sections of buffered formalin-fixed, paraffin-embedded tissue and monoclonal or polyclonal antibodies. There were significant relationships between negative ER and positive EGF-R or TGF-α; positive EGF-R and TGF-α; positive EGF-R and c-erbB-2; and positive c-erbB-2 and TGF-α. The single changes which were the negative ER and the positive c-erbB-2 correlated with histological grade and mitotic index. Co-expression of EGF-R and TGF-α correlated with positive nodal status. Therefore, the present investigation indicates that the negative ER, single expression of c-erbB-2 and co-expression of EGF-R and TGF-α are important markers which contribute indirectly to prognosis, which reconfirms previous findings on the former two while adding the new finding that immuno-histochemical demonstration of expression of EGF-R and TGF-α may provide useful information for selecting the appropriate treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ali IU, Campbell G, Lidereau R, Callahan R (1988) Amplification of c-erbB-2 and aggressive human breast tumors? Science 240:1795–1796

    Google Scholar 

  • Baak JPA, Dop HV, Kurver PHJ, Hermans J (1985) The value of morphometry to classic prognosticators in breast cancer. Cancer 56:374–382

    Google Scholar 

  • Berger MS, Locher GW, Saurer S, Gullick WJ, Waterfield MD, Groner B, Hynes NE (1988) Correlation of c-erbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading. Cancer Res 48:1238–1243

    Google Scholar 

  • Bloom HGJ, Richardson WW (1957) Histologic grading and prognosis in breast cancer. Br J Cancer 11:655–669

    Google Scholar 

  • Borg A, Tandon AK, Sigurdsson H, Clark GM, Ferno M, Fuqua SAW, Killander D, McGuire WL (1990) HER-2/neu amplification predicts poor survival in node-positive breast cancer. Cancer Res 50:4332–4337

    Google Scholar 

  • Dazzi H, Hasleton PS, Thatcher N, Barnes DM, Wilkes S, Swindell R, Lawson RAM (1989) Expression of epidermal growth factor receptor (EGF-R) in non-small cell lung cancer. Use of archival tissue and correlation of EGF-R with histology, tumour size, node status and survival. Br J Cancer 59:746–749

    Google Scholar 

  • Derynck R (1986) Transforming growth factor-α: structure and biological activities. J Cell Biochem 32:203–204

    Google Scholar 

  • Dickson RB, Bates SE, Mcmanaway ME, Lippman ME (1986) Characterization of estrogen responsive transforming activity in human breast cancer cell lines. Cancer Res 46:1707–1713

    Google Scholar 

  • Dotzlaw H, Miller T, Karvelas J, Murphy LC (1990) Epidermal growth factor gene expression in human breast cancer biopsy samples: relation to estrogen and progesterone receptor gene expression. Cancer Res 50:4204–4208

    Google Scholar 

  • Gullick WJ, Downward J, Parker PJ, Whittle N, Kris R, Schlessinger J, Ullrich A, Waterfield MD (1985) The structure and function of EGFr studied by using anti-synthetic peptide antibodies. Proc R Soc Lond 226:127–134

    Google Scholar 

  • Gullick WJ, Marsden JJ, Whittle N, Ward B, Bobrow L, Waterfield MD (1986) Expression of epidermal growth factor receptors on human cervical, ovarian, and vulval carcinomas. Cancer Res 46:285–292

    Google Scholar 

  • Gullick WJ, Berger MS, Bennett PLP, Rothbard JB, Waterfield MD (1987) Expression of the c-erbB-2 protein in normal and transformed cells. Int J Cancer 40:246–254

    Google Scholar 

  • Gusterson BA, Machin LG, Gullick WJ, Gibbs NM, Powles TJ, Elliott C, Ashley S, Monaghan P, Harrison S (1988) c-erbB-2 expression in benign and malignant breast disease. Br J Cancer 58:453–457

    Google Scholar 

  • Jungsil Ro, Naggar A, Ro JY, Blick M, Frye D, Fraschini G, Fritsche H, Hortobagyi G (1989) c-erbB-2 Amplification in node-negative human breast cancer. Cancer Res 49:6941–6944

    Google Scholar 

  • King CR, Kraus MH, Aaronson SA (1985) Amplification of a novel v-erbB-related gene in human mammary carcinoma. Science 229:974–976

    Google Scholar 

  • Knight WAIII, Livingston RB, Gregory EJ, McGuire WL (1977) Estrogen receptor as an independent prognostic factor for early recurrence in breast cancer. Cancer Res 37:4669–4671

    Google Scholar 

  • Marquardt H, Hunkapiller MW, Hood LE, Twardzik DR, De Larco JE, Stephenson JR, Todaro GJ (1983) Transforming growth factors produced by retrovirus-transformed rodent fibroblasts and human melanoma cells: amino acid sequence homology with epidermal growth factor. Proc Natl Acad Sci USA 80:4684–4688

    Google Scholar 

  • Matsumoto K, Ochi H, Nomura Y, Takatani O, Izuo M, Okamoto R, Sugano H (1978) Progesterone and estrogen receptors in Japanese breast cancer. In: McGuire WL (ed) Hormones, receptors, and breast cancer. Raven Press, New York, pp 43–58

    Google Scholar 

  • McGuire WL, Dickson RB, Osborne CK, Salomon D (1988) The role of growth factors in breast cancer. A panel discussion. Breast Cancer Res Treat 12:159–166

    Google Scholar 

  • Meyers SL, O'Brien MT, Smith T, Dudley JP (1990) Analysis of theint-1,int-2, c-myc, andneu oncogene in human breast carcinoma. Cancer Res 50:5911–5918

    Google Scholar 

  • Mizukami Y, Nonomura A, Yamada T, Kurumaya H, Hayashi M, Koyasaki N, Taniya T, Noguchi M, Nakamura S, Matubara F (1990) Immunohistochemical demonstration of growth factors, TGF-α, TGF-β, IGF-I andneu oncogene product in benign and malignant human breast tissues. Anticancer Res 10:1115–1126

    Google Scholar 

  • Okamoto S, Oka T (1984) Evidence for physiological function of epidermal growth factors: pregestational sialoadenectomy in mice decreases milk production and increases offspring mortality during lactation period. Proc Natl Acad Sci USA 81:6059–6063

    Google Scholar 

  • Osborne CK, Artega CL (1990) Autocrine and paracrine growth regulation of breast cancer: clinical implications. Breast Cancer Res Treat 15:3–11

    Google Scholar 

  • Real FX, Retting WJ, Chesa PG, Melamed MR, Old LJ, Mendelsohn J (1986) Expression of epidermal growth factor receptor in human cultures cells and stage of differentiation. Cancer Res 46:4726–4731

    Google Scholar 

  • Reynolds FH Jr, Todaro GJ, Fryling C, Stephenson JR (1983) Human transforming growth factors induce tyrosine phosphorylation of EGF receptors. Nature 292:259–262

    Google Scholar 

  • Roberts MM, Rubens RD, King RJB (1978) Oestrogen receptors and the response to endocrine therapy in advanced breast cancer. Br J Cancer 38:431–436

    Google Scholar 

  • Sainsbury JRC, Malcolm AJ, Appleton DR, Farndon JR, Harris AL (1987a) Presence of epidermal growth factor receptor as an indicator of poor prognosis in patients with breast cancer. J Clin Pathol 38:1225–1228

    Google Scholar 

  • Sainsbury JRC, Farndon JR, Needham GK, Malcolm AJ, Harris AL (1987b) Epidermal-growth-factor receptor status as predictor of early recurrence of and death from breast cancer. Lancet 1:1398–1402

    Google Scholar 

  • Schechter AL, Hung MC, Vaidyanathan L, Weinberg RA, Feng TLY, Francke U, Ullrich A, Coussens L (1985) Theneu gene: anerbB-homologous gene distinct from and unlinked to the gene encoding the EGF-receptor. Science 229:976–978

    Google Scholar 

  • Semba K, Kamata N, Toyoshima K, Yamamoto T (1985) A verbB-related proto-oncogene, c-erbB-2, is distinct from the cerbB-1/epidermal growth factor receptor gene and is amplified in a human salivary gland adenocarcinoma. Proc Natl Acad Sci USA 82:6497–6501

    Google Scholar 

  • Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–183

    Google Scholar 

  • Sorvillo JM, McCormack ES, Yanez L, Valenzuela D, Reynolds FH (1990) Preparation and characterization of monoclonal antibodies specific for human transforming growth factor. Oncogene 5:377–386

    Google Scholar 

  • Sporn MB, Todaro GJ (1980) Autocrine secretion and malignant transformation of cells. N Engl J Med 303:878–880

    Google Scholar 

  • Spyratos F, Delarue JC, Andrieu C, Lidereau R, Champeme MH, Hacene K, Brunet M (1990) Epidermal growth factors and prognosis in primary breast cancer. Cancer Res Treat 17:83–89

    Google Scholar 

  • Taylor JM, Mitchell WM, Cohen S (1972) Epidermal growth factor: physical and chemical properties. J Biol Chem 247:5928–5934

    Google Scholar 

  • Thor AD, Schwartz LH, Koerner FC, Edgerton SM, Skates SJ, Yin S, McKenzie SJ, Panicali DL, Marks PJ, Fingert HJ, Wood WC (1989) Analysis of c-erbB-2 expression in breast carcinoma with clinical follow-up. Cancer Res 49:7147–7152

    Google Scholar 

  • Tsuda H, Hirohashi S, Shimosato Y, Hirota T, Tsugane S, Yamamoto H, Miyajima N, Toyoshima K, Yamamoto T, Yokota J, Yoshida T, Sakamoto H, Terada M, Sugimura T (1989) Correlation between long-term survival in breast cancer patients and amplification of two putative oncogene-coamplification units:hst-1/int-2 and c-erbB-2/ear-1. Cancer Res 49:3104–3108

    Google Scholar 

  • Uehara T, Kaneko Y, Kanda N, Yamamoto T, Higashi Y, Nomoto C, Izumo T, Takayama S, Sakurai M (1990) c-erbB-2 and c-erbA-1 (ear-1) gene amplification and c-erbB-2 protein expression in Japanese breast cancers: their relationship to the histology and other disease parameters. Jpn J Cancer Res 81:620–624

    Google Scholar 

  • Venter DJ, Tuzi NL, Kumar S, Gullick WJ (1987) Overexpression of the c-erbB-2 oncoprotein in human breast carcinomas: immunohistological assessment correlates with gene amplification. Lancet II:69

    Google Scholar 

  • Vijver MJ van de, Peters JL, Mooi WJ, Lomans J, Palesio O, Nesse R (1988) 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 319:1239–1245

    Google Scholar 

  • Wright C, Angus B, Nicholson S, Sainbury JRC, Cairns J, Gullick WJ, Kelly P, Harris AL, Horne CHW (1989) Expression of c-erbB-2 oncoprotein: a prognostic indicator in human breast cancer. Cancer Res 49:2087–2090

    Google Scholar 

  • Yamada Y, Yoshimoto M, Murayama Y, Ebuchi M, Mori S, Yamamoto T, Sugano H, Toyoshima K (1989) Association of elevated expression of the c-erbB-2 protein with spread of breast cancer. Jpn J Cancer Res 80:1192–1198

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, 890, Kagoshima, Japan

    Yoshihisa Umekita, Kazumi Kuriwaki, Takashi Takasaki, Aichi Yoshida & Hiroki Yoshida

  2. Sagara Hospital, 3-31 Matsubara-cho, 890, Kagoshima, Japan

    Nobumasa Enokizono & Yoshiatsu Sagara

Authors
  1. Yoshihisa Umekita
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nobumasa Enokizono
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoshiatsu Sagara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kazumi Kuriwaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takashi Takasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Aichi Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hiroki Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Umekita, Y., Enokizono, N., Sagara, Y. et al. Immunohistochemical studies on oncogene products (EGF-R, c-erbB-2) and growth factors (EGF, TGF-α) in human breast cancer: their relationship to oestrogen receptor status, histological grade, mitotic index and nodal status. Vichows Archiv A Pathol Anat 420, 345–351 (1992). https://doi.org/10.1007/BF01600214

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01600214

Key words

Search

Navigation