Skip to main content
SpringerLink
Log in

Proliferative indices and oncoprotein expression in benign and malignant breast biopsies

  • Original Articles
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background: Prognostic factors are used routinely in the management of breast cancer. However, their potential for identifying precursor malignant lesions has not been assessed.

Methods: We have examined 285 breast biopsy specimens (140 benign, 145 malignant) for DNA ploidy, S-phase fraction, Ki-67 nuclear antigen proliferative indices, and HER-2/neu and epidermal growth factor receptor oncoproteins.

Results: When proliferative indices were compared between the benign and malignant groups, differences were noted for DNA ploidy, S-phase fraction, and cell cycling index (p<0.0005). When the benign nonproliferative specimens were compared with the atypical/proliferative benign specimens, proliferative indices failed to show any differences. When the specific subset of proliferative/atypical benign breast tissue was compared with the malignant specimens, DNA index, S-phase fraction, and cell cycling index showed significant differences. The mean for epidermal growth factor receptor was greater in the non-proliferative group but not statistically significant (p<0.1). HER-2/neu oncoprotein failed to show any differences between the benign and malignant groups. Within the atypical benign group, Ki-67 correlated strongly with S-phase fraction and HER-2/neu (p<0.01).

Conclusions: We have demonstrated that proliferative indices can differentiate between benign and malignant breast tissues but not among specific subgroups. In addition, epidermal growth factor may differentiate between nonproliferative and proliferative/atypical benign biopsy results. Oncoprotein determination, ploidy, and DNA proliferative indices may be useful in defining malignant and benign breast disease but are not useful in distinguishing between benign and malignant breast disease with an increased likelihood for malignant transformation.

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

  1. Beerman H, Kluin P, Hermans J, Van de Velde C, Cornelissse C. Prognostic significance of DNA-ploidy in a series of 690 primary breast cancer patients.Int J Cancer 1990;45:34–9.

    CAS  PubMed  Google Scholar 

  2. Clark G, McGuire W. Steroid receptors and other prognostic factors in primary breast cancer.Semin Oncol 1988;15:20–28.

    CAS  PubMed  Google Scholar 

  3. Clark G, Dressler L, Owens M. Prediction of relapse or survival in patients with node-negative breast cancer by DNA flow cytometry.N Engl J Med 1989;320:627–9.

    CAS  PubMed  Google Scholar 

  4. Clark G, McGuire W. New biologic prognostic factors in breast cancer.Oncology 1989;:49–54.

  5. Perez R, Pascual M, Macias A. Epidermal growth factor receptors in human breast cancer.Breast Cancer Res Treat 1984;4:189–94.

    CAS  PubMed  Google Scholar 

  6. Slamon D, Clark G, Wong S. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.Science 1987;235:177–8.

    CAS  PubMed  Google Scholar 

  7. Van de Vijver M, Peterse J, Mooi W. Neu-protein overexpression in breast cancer.N Engl J Med 1988;319:781–4.

    Google Scholar 

  8. Dupont W, Page D. Risk factors for breast cancer in women with proliferative breast disease.N Engl J Med 1985;312:146–51.

    CAS  PubMed  Google Scholar 

  9. Elston C, Ellis I. Pathology and breast screening.Histopathology 1990;15:109–18.

    Google Scholar 

  10. Gump F, Jicha D, Ozello L. Ductal carcinoma in situ (DCIS): a revised concept.Surgery 1987;102:790–5.

    CAS  PubMed  Google Scholar 

  11. Parl F, Dupont W. A retrospective cohort study of histologic risk factors in breast cancer patients.CA 1982;50:2410–6.

    CAS  Google Scholar 

  12. Reichert C, Moshiri S, Austin R, Norris H. Gross and microscopic pathology of the female breast: prognostic variables and current approaches to primary breast cancer diagnosis. In: Lippman M, Lichter A, Danfort JDN, eds.Diagnosis and management of breast cancer. Philadelphia, PA: WB Saunders, 1988:22–49.

    Google Scholar 

  13. Gerdas J, Schwab U, Lemke H, Stein H. Production of mouse monoclonal antibody reactive with human nuclear antigen associated with cell proliferation.Int J Cancer 1983;31:13–20.

    Google Scholar 

  14. Zehr R, Bauwer T, Marks K, Weltvreden A. Ki-67 and grading of malignant fibrous histocytomas.CA 1990;66:1984–90.

    CAS  Google Scholar 

  15. Bacus S, Goldschmikdt R, Chin D, Moran G, Weinberg D, Bacus J. Biological grading of breast cancer using antibodies of proliferating cells and other markers.Am J Pathol 1989;135;783–92.

    CAS  PubMed  Google Scholar 

  16. Barnard N, Hall P, Lemoine N, Kadar N. Proliferative index in breast carcinoma determined in situ by Ki-67 immuno-staining and its relationship to clinical and pathological variables.J Pathol 1987;152:287–95.

    Article  CAS  PubMed  Google Scholar 

  17. Pavelic Z, Pavelic L, Lower E, et al. c-myc, c-erbB-2 and Ki-67 expression in normal breast tissue and in invasive and noninvasive breast carcinoma.Cancer Res 1992;52:2597–602.

    CAS  PubMed  Google Scholar 

  18. Slamon D, Godolphin W, Jones L. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer.Science 1989;244:707–12.

    CAS  PubMed  Google Scholar 

  19. Tandon A, Clark G, Cahmness G. Her-2/neu oncogene protein and prognosis in breast cancer.J Clin Oncol 1988;7:1120–4.

    Google Scholar 

  20. Carter C, Corle D, Micozzi M. A prospective study of the development of breast cancer in 16,692 women with benign breast disease.Am J Epidemiol 1988;128:467–77.

    CAS  PubMed  Google Scholar 

  21. Page D, Dupont W. Histopathologic risk factors for breast cancer in women with benign disease.Semin Surg Oncol 1988;4:213–7.

    CAS  PubMed  Google Scholar 

  22. Page D, Dupont W. Anatomic markers of human premalignancy and risk of breast cancer.CA 1990;66:1326–35.

    CAS  Google Scholar 

  23. McGuire W. Prognostic factors in primary breast cancer.Cancer Surg 1986;5:527–31.

    CAS  Google Scholar 

  24. McGuire W, Clark G. Prognostic factors for recurrence and survival in axillary node negative breast cancer.J Steroid Biochem Mol Biol 1990;7:243–50.

    Google Scholar 

  25. Silvestrini R, Daidon M, Di Fronzo G. Prognostic implication of labelling index versus oestrogen receptors and tumour size in node-negative breast cancer.Breast Cancer Res Treat 1986;7:161–4.

    Article  CAS  PubMed  Google Scholar 

  26. Bates S, Davidson N, Valerius E. Expression of transforming growth factor alpha and its mRNA in human breast cancer: its regulation by estrogen and its possible functional significance.Mol Endocrinol 1988;2:543–6.

    CAS  PubMed  Google Scholar 

  27. Garcia I, Dietrich P, Aapro M, Vauthier G, Vadas L, Engel E. Genetic alterations of c-myc, c-erbB-2, and c-Ha-ras protooncogenes and clinical associations in human breast carcinomas.Cancer Res 1989;49:6675–9.

    CAS  PubMed  Google Scholar 

  28. Thorpe S, Rochefort, Garcia M. Association between high concentrations of Mr 52,000 cathepsin D and poor prognosis in primary breast cancer.Cancer Res 1989;49:6008–12.

    CAS  PubMed  Google Scholar 

  29. Dickson R, Lippmann M. Estrogen regulation of growth and polypeptide growth factor secretion in human breast carcinoma.Endocr Rev 1986;8:29–43.

    Google Scholar 

  30. Bouzubar N, Walker K, Griffiths K. Ki67 immuno-staining in primary breast cancer: pathological and clinical associations.Br J Cancer 1989;59:943–7.

    CAS  PubMed  Google Scholar 

  31. Cornelisse C, van de Velde C, Caspers R. DNA ploidy and survival in breast cancer patients.Cytometry 1987;8:225–30.

    Article  CAS  PubMed  Google Scholar 

  32. Dressler L, Seamer L, Owens M. DNA flow cytometry and prognostic factors in 1331 frozen breast cancer specimens.CA 1988;61:420–4.

    CAS  Google Scholar 

  33. Quinn C, Wright N. The clinical assessment of proliferation and growth in human tumours: evaluation of methods and applications as prognostic variables.J Pathol 1990;160:93–102.

    Article  CAS  PubMed  Google Scholar 

  34. Tubiana M, Pejovic M, Chavaudra N. The long-term prognostic significance of the thymidine labelling index in breast cancer.Int J Cancer 1984;33:441–8.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Mount Sinai Medical Center, New York, New York

    Ira Bleiweiss MD

  2. Dianon Systems, Inc., Stratford, Connecticut, USA

    Cheryl Hayden PhD

  3. Division of Surgical Oncology, Department of Surgery, Mount Sinai Medical Center, 1 Gustave L. Levy Place, Box 1259, 10029, New York, NY, USA

    Steven T. Brower MD, Paul I. Tartter MD, Sharmila Ahmed BA, Cristina M. Brusco BA & Kathi Bossolt MD

Authors
  1. Steven T. Brower MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul I. Tartter MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sharmila Ahmed BA
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cristina M. Brusco BA
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kathi Bossolt MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cheryl Hayden PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ira Bleiweiss MD
    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

Brower, S.T., Tartter, P.I., Ahmed, S. et al. Proliferative indices and oncoprotein expression in benign and malignant breast biopsies. Annals of Surgical Oncology 2, 416–423 (1995). https://doi.org/10.1007/BF02306374

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02306374

Key Words

Search

Navigation