Skip to main content
Log in

Immunohistochemical determination and grading of CerbB-2 expression in breast cancer: correlation with interpectoral, apical nodal involvement and other prognostic factors

  • Research Article
  • Published:
Central European Journal of Medicine

Abstract

We aimed to investigate the correlation between quantitative CerbB-2 expressions with conventional prognostic factors, and distinct nodal involvement in patients with invasive breast carcinoma. One hundred fifty seven consecutive breast carcinoma patients were retrospectively analysed. Level I–II, Level III, and Rotter (Interpectoral) group lymph nodes were separately examined and recorded. For each patient estrogen receptor (ER), progesteron receptor (PR), CerbB-2, P53 status were defined using immunohistochemistry. Age, tumor localisation, menopausal status, grade and the presence of intraductal component were also recorded. CerbB-2 expression did not correlate with age, localisation and menopausal status. There was a reverse, but weak correlation with tumor size and CerbB-2 expression (p=0.034). In subgroup analysis of CerbB-2 positive cases, the magnitude of CerbB-2 positivity did not correlate with tumor size (p=0.551). In univariate analysis CerbB-2 expression did not correlate with nodal involvement in Level I-II, and Rotter. In subgroup analysis of patients with positive CerbB-2, positivity of CerbB-2 linearly increased with the number of positive lymph nodes in Level I-II, and this difference was significant (p=0,039). There was a significant correlation between CerbB-2 expression and Level III nodal metastases (p=0.005). But this correlation was not significant among CerbB-2 positive patients (p=0.82). P53, PR positivity and the presence of intraductal component did not differ according to oncogene expression. We detected a reverse correlation with ER positivity and CerbB-2 positivity (p=0.011). It is concluded that quantitative expression of CerbB2 positivity increases with nodal involvement in Level I–II axillary lymph nodes, and ER. Also, CerbB-2 positivity is more common among patients with Level III lymph node metastases.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. R.T. Greenlee, T. Murray, S. Bolden and P.A. Wingo: “Cancer Statistics”, CA Cancer. J. Clin., Vol. 50, (2000), pp. 7–33.

    PubMed  CAS  Google Scholar 

  2. D.L. Page: “Prognosis and breast cancer: recognition of lethal and favourable prognostic types”, Am. J. Surg. Pathol., Vol. 15, (1991), pp. 334–349.

    Article  PubMed  CAS  Google Scholar 

  3. N.J. Bundred: “Prognostic and predictive factors in breast cancer”, Cancer. Treat. Rev., Vol. 27, (2001), pp. 137–142.

    Article  PubMed  CAS  Google Scholar 

  4. E. Tzahar and Y. Yarden: “The ErbB-2/HER2 oncogenic receptor of adenocarcinomas: from orphanhood to multiple stromal ligands”, Biochim. Biophys. Acta., Vol. 1377, (1998), pp. 25–37.

    Google Scholar 

  5. D.F. Hayes and A.D. Thor: “C-erbB-2 in breast cancer: Development of a clinically useful marker”, Semin. Oncol., Vol. 29, (2002), pp. 231–245.

    Article  PubMed  CAS  Google Scholar 

  6. Y. Yarden: “Biology of HER2 and its importance in breast cancer”, Oncology, Vol. 61, (2001), pp. 1–13.

    Article  PubMed  CAS  Google Scholar 

  7. C. Isaacs, V. Stearns and D.F. Hayes: “New prognostic factors for breast cancer recurrence”, Semin. Oncol., Vol. 28, (2001), pp. 53–67.

    Article  PubMed  CAS  Google Scholar 

  8. J.S. Huston and A.J. George: “Engineered antibodies take center stage”, Hum. Antibodies., Vol. 10 (2001), pp. 127–142.

    PubMed  CAS  Google Scholar 

  9. D J. Slamon, B. Leyland-Jones, S. Shak, H. Fuchs, V. Paton, A. Bajamonde, T. Fleming, W Eiermann, J. Wolter, M. Pegram, J. Baselga and L. Norton: “Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2”, N. Engl. J. Med., Vol. 344, (2001), pp. 783–792.

    Article  PubMed  CAS  Google Scholar 

  10. D.J. Slamon, G.M. Clark, S.G. Wong, W.J. Levin, A. Ullrich and W.L. McGuire: “Human breast cancer: correlation of relapse and survival with amplification of HER2/neu oncogene”, Science., Vol. 235, (1987), pp. 177–182.

    Article  PubMed  CAS  Google Scholar 

  11. O. Stal, S. Sullivan, S. Wingren, L. Skoog, L.E. Rutqvist, J.M. Carstensen and B. Nordenskjold: “CerbB-2 expression and benefit from adjuvant chemotherapy and radiotherapy of breast cancer”, Eur. J. Cancer., Vol. 31, (1995), pp. 2185–2190.

    Article  Google Scholar 

  12. S. Kaptain, L.K. Tan and B. Chen: “HER2/neu and breast cancer”, Diagn. Mol. Pathol., Vol. 10, (2001), pp. 139–152.

    Article  PubMed  CAS  Google Scholar 

  13. A. Tervahauta, M. Eskelinen, S. Syrjanen, P. Lipponen, P. Pajarinen and K. Syrjanen: “Immunohistochemical demonstration of CerbB-2 oncoprotein expression in female breast cancer and its prognostic significance”, Anticancer. Res., Vol. 11, (1991), pp. 1677–1681.

    PubMed  CAS  Google Scholar 

  14. F. Rilke, M.I. Colgagni, N. Cascinelli, S. Andreola, M.T. Baldini, R. Bufalino, G. Della Porta, S. Menard, M.A. Pierotti and A. Testori: “Prognostic significance of HER2/neu expression in breast cancer and its relationship to other prognostic factors”, Int. J. Cancer., Vol. 49, (1991), pp. 44–49.

    PubMed  CAS  Google Scholar 

  15. S. Tsutsui, S. Ohno, S. Murakami, Y. Hachitanda and S. Oda: “Prognostic value of CerbB-2 expression in breast cancer”, J. Surg. Oncol., Vol. 79, (2002), pp. 216–223.

    Article  PubMed  CAS  Google Scholar 

  16. A. Borg, B. Baldetrop, M. Ferno, D. Killander, H. Olsson and H. Sigurdsson: “ERBB2 amplification in breast cancer with high rate of proliferation”, Oncogene., Vol. 6, (1991), pp. 137–143.

    PubMed  CAS  Google Scholar 

  17. H. Schimmelpenning, E.T. Eriksson, U.G. Falkmer, L.E. Rutqvist, H. Johansson, A. Fallenius and G.U. Auer: “Prognostic significance of immunohistochemical CerbB-2 proto-oncogene expression and nuclear DNA content in human breast cancer”, Eur. J. Surg. Oncol., Vol. 18, (1992), pp. 530–537.

    PubMed  CAS  Google Scholar 

  18. S.E. Singletary, C. Allred, P. Ashley, L.W. Bassett, D. Berry, K.I. Bland, P.I. Borgen, G.M. Clark, S.B. Edge, D.F. Hayes, L.L. Hughes, R.V. Hutter, M. Morrow, D.L. Page, A. Recht, R.L. Theriault, A. Thor, D.L. Weaver, H.S. Wieand and F.L. Greene: “Staging System for breast cancer: revisions for the 6th edition of the AJCC Cancer Staging Manuel”, Surg. Clin. North. Am., Vol. 83, (2003), pp. 803–819.

    Article  PubMed  Google Scholar 

  19. L.A. Newman, H.M. Kuerer, B. Fornage, N. Mirza, K.K. Hunt, M.I. Ross, F.C. Ames, A.U. Buzdar and S.E. Singletary: “Adverse prognostic significance of infraclavicular lymph nodes detected by ultrasonography in patients with locally advanced breast cancer”, Am. J. Surg., Vol. 181, (2001), pp. 313–318.

    Article  PubMed  CAS  Google Scholar 

  20. I.K. Komenaka, V.P. Bauer, F.R. Schnabel, K.A. Joseph, E. Horowitz, B.A. Ditkoff and M.B. El-Tamer: “Interpectoral nodes as the initial site of recurrence in breast cancer”, Arch. Surg., Vol. 139, (2004), pp. 175–178.

    Article  PubMed  Google Scholar 

  21. S.H. Estourgie, O.E. Nieweg, R.A. Olmos, E.J. Rutgers and B.B. Kroon: “Lymphatic drainage patterns from the breast”, Ann. Surg., Vol. 239, (2004), pp. 232–237.

    Article  PubMed  Google Scholar 

  22. D. Marx, A. Schauer, C. Reiche, A. May, L. Ummenhofer, A. Reles, H. Rauschecker, R. Sauer and M. Schumacher: “CerbB-2 expression in correlation to other biological parameters of breast cancer”, J. Cancer. Res. Clin. Oncol., Vol. 116, (1990), pp. 15–20.

    Article  PubMed  CAS  Google Scholar 

  23. A. Jukkola, R. Bloigu, Y. Soini, E.R. Savolainen, K. Holli and G. Blanco: “CerbB-2 positivity is a factor for poor prognosis in breast cancer and poor response to hormonal or chemotherapy treatment in advanced disease”, Eur. J. Cancer., Vol. 37, (2001), pp. 347–354.

    Article  PubMed  CAS  Google Scholar 

  24. S. Sjögren, M. Inganas, A. Lindgren, L. Holmberg and J. Bergh: “Prognostic and predictive value of CerbB-2 overexpression in primary breast cancer, alone and in combination with other prognostic markers”, J. Clin. Oncol., Vol. 16, (1998), pp. 462–469.

    PubMed  Google Scholar 

  25. M. Bebenek, J.K. Bar, A. Harlonzinska and P. Sedlaczek: “Prospective studies of P53 and CerbB-2 expression in relation to clinicopathological parameters of human ductal breast cancer in the second stage of clinical advancement”, Anticancer. Res., Vol. 18, (1998), pp. 619–623.

    PubMed  CAS  Google Scholar 

  26. M. Samur, S. Karaveli, H. Bozcuk, E. Pestereli, M. Ozdogan, M. Yildiz, M. Artac and B. Savas: “A novel method of reporting CerbB-2 overexpression: Correlation with grade but not with other prognostic parameters in breast cancer”, Turkish. J. Med. Sci. 2003, Vol. 33, pp. 363–368.

    CAS  Google Scholar 

  27. A. Barbati, E.V. Cosmi, A. Sidoni, P. Collini, M.G. Porpora, I. Ferri, M. Luthy, V. Lauro and E. Bucciarelli: “Value of CerbB-2 and P53 oncoprotein co-overexpression in human breast cancer”, Anticancer. Res., Vol. 17, (1997), pp. 401–405.

    PubMed  CAS  Google Scholar 

  28. M. Saceda, T.W. Grunt, R. Colomer, M.E. Lippman, R. Lupu and M.B. Martin: “Regulation of estrogen receptor concentration and activity by an Erb/HER ligand in breast carcinoma cell lines”, Endocrinol., Vol. 137, (1996), pp. 4322–4330.

    Article  CAS  Google Scholar 

  29. S.A. Fuqua, S.D. Fitzgerald, D.C. Allred, R.M. Elledge, Z. Nawaz, D.P. McDonnell, B.W. O’Malley, G.L. Greene and W.L. McGuire: “Inhibition of estrogen receptor action by a naturally occurring variant in human breast tumors”, Cancer. Res., Vol. 52, (1992) pp. 483–486.

    PubMed  CAS  Google Scholar 

  30. P.P. Rosen, M.L. Lesser, C.D. Arroyo, M. Cranor, P. Borgen and L. Norton: “Immunohistochemical detection of HER-2/neu in patients with axillary lymph node negative breast carcinoma. A study of epidemiologic risk factors, histologic features, and prognosis”, Cancer., Vol. 75, (1995), pp. 1320–1326.

    Article  PubMed  CAS  Google Scholar 

  31. H.J. Lipponen, S. Aaltomaa, S. Syrjanen and K. Syrjanen: “CerbB-2 oncogene related to P53 expression, cell proliferation and prognosis in breast cancer”, Anticancer. Res., Vol. 13, (1993), pp. 1147–1152.

    PubMed  CAS  Google Scholar 

  32. S.W. Beenken, W.E. Grizzle, R.D. Crowe, M.G. Conner, H.L. Weiss, M.T. Sellers, H. Krontiras, M.M. Urist and K.I. Bland: “Molecular biomarkers for breast cancer prognosis: co-expression of CerbB-2 and P53”, Ann. Surg., Vol. 233, (2001), pp. 630–638.

    Article  PubMed  CAS  Google Scholar 

  33. L.L. Nakopoulou, A. Alexiadou, G.E. Theodoropoulos, A.C. Lazaris, A. Tzonou and A. Keramopoulos: “Prognostic significance of the co-expression of P53 and CerbB-2 proteins in breast cancer”, J. Pathol., Vol. 179, (1996), pp. 31–38.

    Article  PubMed  CAS  Google Scholar 

  34. J. Jacquemier, F. Penault-Llorca, P. Viens, G. Houvenaeghel, J. Hassoun, M. Torrente, J. Adelaide and D. Birnbaum: “Breast cancer response to adjuvant chemotherapy in correlation with erbB2 and p53 expression”, Anticancer. Res., Vol. 14, (1994), pp. 2773–2778.

    PubMed  CAS  Google Scholar 

  35. S. Menard, P. Casalini, S. Pilotti, N. Cascinelli, F. Rilke and M.I. Colnaghi: “No additive impact on patient survival of the double alteration of P53 and CerbB-2 in breast carcinomas”, J. Natl. Cancer. Inst., Vol. 88, (1996), pp. 1002–1003.

    Article  PubMed  CAS  Google Scholar 

  36. C. Lohrisch and M. Piccart: “An overview of HER”, Semin. Oncol., Vol. 28, (2001), pp. 3–11.

    Article  PubMed  CAS  Google Scholar 

  37. X. Jing, K. Kakudo, M. Murakami, Y. Nakamura, M. Nakamura, T. Yokoi, Q. Yang, S. Oura and T. Sakurai: “Intraductal spread of invasive breast carcinoma has a positive correlation with CerbB-2 overexpression and vascular invasion”, Cancer., Vol. 86, (1999), pp. 439–448.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

About this article

Cite this article

Çelik, A., Ebru Arabacı, I., Erkorkmaz, U. et al. Immunohistochemical determination and grading of CerbB-2 expression in breast cancer: correlation with interpectoral, apical nodal involvement and other prognostic factors. cent.eur.j.med 2, 1–11 (2007). https://doi.org/10.2478/s11536-007-0006-6

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.2478/s11536-007-0006-6

Keywords

Navigation