Skip to main content
SpringerLink
Log in

Comparison of PCNA/cyclin immunohistochemistry with flow cytometric S-phase fraction in breast cancer

  • Report
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Kinetic index determined by enumeration of neoplastic cells positive for proliferative cell nuclear antigen (PCNA) in 70 breast carcinomas (avidin-biotin immunoperoxidase technique) was compared to synthesis-phase fraction (S-phase, or SPF) values obtained by flow cytometry (FCM) using a multiparametric, 2 color method (dual-label propidium iodide/cytokeratin-FITC). The percent PCNA positive tumor cells (12.5% mean, range 1–28%) was significantly greater in aneuploid tumors (14.2% mean, N=35) compared to diploid range tumors (10.7% mean, N=35) (p<0.05), and was correlated with SPF derived from ungated DNA histograms (12.5% mean ± 5.5%, r=0.45, p<0.001). Marginally stronger statistical correlations were observed between the PCNA index and SPF values calculated from cytokeratin-gated (15.8% mean, r=0.53, p<0.001) DNA histograms or from SPF values obtained following linear baseline debris subtraction (mean=8.1%, r=0.48, p<0.001). Significant associations were identified between PCNA index and prognostically important clinicopathologic parameters including nuclear grade (p=0.014), presence of necrosis (p=0.005), and angiolymphatic invasion (p=0.003). We conclude: 1) PCNA index is comparable to FCM SPF and correlates with factors of known prognostic importance in carcinoma of the breast; 2) baseline debris and contaminating events derived from non-epithelial cells both represent significant artifacts in proliferative fraction estimates derived from FCM DNA histograms; and 3) multiparametric analysis may represent one means of improving the specificity and clinical value of FCM SPF determinations.

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. Baisch H, Beck HP, Christensen IJ, Hartmann NR, Fried J, Dean PN, Gray JW, Johnston DA, White RA, Nicolini C, Zeitz S, Watson JV: A comparison of mathematical methods for the analysis of DNA histograms obtained by flow cytometry. Cell Tissue Kinet 15: 235, 1982

    PubMed  Google Scholar 

  2. Clark GM, Dressler LG, Owens MA, Pounds G, Oldaker T, McGuire WL: Prediction of relapse or survival in patients with node-negative breast cancer by DNA flow cytometry. N Engl J Med 320: 627–633, 1989

    PubMed  Google Scholar 

  3. Dawson AE, Norton JA, Weinberg DS: Comparative assessment of proliferation and DNA content in breast carcinoma by image analysis and flow cytometry. Am J Pathol 136: 1115–1124, 1990

    PubMed  Google Scholar 

  4. Feichter G, Czech W, Haag D, Goerttler K, Futterman G, Loehrke H, Abel U: Comparison of S-phase fractions measured by flow cytometry and autoradiography in human transplant tumors. Cytometry 9: 605–611, 1988

    PubMed  Google Scholar 

  5. Fisher B, Gunduz N, Costantino J, Fisher ER, Redmond Cet al.: DNA flow cytometric analysis of primary operable breast cancer. Cancer 68: 1465–1475, 1991

    PubMed  Google Scholar 

  6. Garcia RL, Coltrera MD, Gown AM: Analysis of proliferative grade using anti-PCNA/cyclin monoclonal antibodies in fixed, embedded tissues [Rapid communication]. Am J Pathol 134: 733, 1989

    PubMed  Google Scholar 

  7. Gerdes J, Lelle RJ, Pickartz H, Heidenreich W, Schwarting R, Kurtsiefer L, Stauch G, Stein H: Growth fractions in breast cancers determinedin situ with monoclonal antibody Ki-67. J Clin Pathol 39: 977–980, 1986

    PubMed  Google Scholar 

  8. Haag D, Feichter G, Goerttler K, Kaufmann M: Influence of systematic errors on the evaluation of the S phase portions from DNA distributions of solid tumors as shown for 328 breast carcinomas. Cytometry 8: 377–385, 1987

    PubMed  Google Scholar 

  9. Hatschek T, Fagerberg G, Stål O, Sullivan SIW, Carstensen Jet al.: Cytometric characterization and clinical course of breast cancer diagnosed in a population-based screening program. Cancer 64: 1074–1081, 1989

    PubMed  Google Scholar 

  10. Isola JJ, Helin HJ, Helle MJ, Kallioniemi O-P: Evaluation of cell proliferation in breast carcinoma: comparison of Ki67 immunohistochemical study, DNA flow cytometric analysis, and mitotic count. Cancer 65: 1180–1184, 1990

    PubMed  Google Scholar 

  11. Kurki P, Ogate K, Tan EM: Monoclonal antibodies to proliferating cells nuclear antigen (PCNA)/cyclin as probes for proliferating cells by immunofluorescence microscopy and flow cytometry. J Immunological Methods 109: 49–59, 1988

    Google Scholar 

  12. McDivitt RW, Stone KR, Craig RB, Meyer JS: A comparison of human breast cancer cell kinetics measured by flow cytometry and thymidine labeling. Lab Invest 52: 287, 1985

    PubMed  Google Scholar 

  13. McGurrin JF, Doria MI Jr, Dawson PJ, Karrison T, Stein HO, Franklin WA: Assessment of tumor cell kinetics by immunohistochemistry in carcinoma of the breast. Cancer 59: 1744, 1987

    PubMed  Google Scholar 

  14. Meyer JS, Coplin MD: Thymidine labeling index, flow cytometric S-phase measurement, and DNA index in human tumors. Am J Clin Pathol 89: 586–595, 1988

    PubMed  Google Scholar 

  15. Meyer JS, Friedman E, McCrate M, Bauer WC: Prediction of early course of breast carcinoma by thymidine labeling. Cancer 51: 1879–1886, 1983

    PubMed  Google Scholar 

  16. Meyer JS, Wittliff JL: Regional heterogeneity in breast carcinoma: Thymidine labelling index, steroid hormone receptors, DNA ploidy. Int J Cancer 47: 213–220, 1991

    PubMed  Google Scholar 

  17. O'Reilly SM, Camplejohn RS, Barnes DM, Milles RR, Rubens RD, Richards MA: Node-negative breast cancer: Prognostic subgroups defined by tumor size and flow cytometry. J Clin Oncol 8: 2040–2046, 1990

    PubMed  Google Scholar 

  18. Tubiana M, Courdi A: Cell proliferation kinetics in human solid tumors: Relation to probability of metastatic dissemination and long-term survival. Radiother Oncol 15: 1–18, 1989

    PubMed  Google Scholar 

  19. Van der Linden JC, Lindeman J, Baak JPA, Meijer CJLM, Herman CJ: The multivariate prognostic index and nuclear DNA content are independent prognostic factors in primary breast cancer patients. Cytometry 10: 56–61, 1989

    PubMed  Google Scholar 

  20. Vielh P, Chevillard S, Mosseri V, Donatini B, Magdelenat H: Ki67 index and S-phase fraction in human breast carcinomas. Am J Clin Pathol 94: 681–686, 1990

    PubMed  Google Scholar 

  21. Visscher DW, Wykes S, Zarbo RJ, Crissman JD: Multiparametric evaluation of flow cytometric synthesis phase fraction determination in dual labelled breast carcinomas. Anal Quant Cytol Histol 13: 246–252, 1991

    PubMed  Google Scholar 

  22. Visscher DW, Zarbo RJ, Greenawald KA, Crissman JD: Prognostic significance of morphological parameters and flow cytometric DNA analysis in carcinoma of the breast. Pathol Ann, Part 1, Vol 25, ed by Rosen PP, Fechner RE. Norwalk, Appleton and Lange, 1990, pp 171–210

  23. Visscher DW, Zarbo RJ, Jacobsen G, Kambouris A, Talpos G, Sakr W, Crissman JD: Multiparametric deoxyribonucleic acid and cell cycle analysis of breast carcinomas by flow cytometry: Clinicopathologic correlations. Lab Invest 62: 370, 1990

    PubMed  Google Scholar 

  24. Waldman F, Balazs M, Matsumura K, Kallioniemi O, Kallioniemi A, Smith Het al.: Interphase cytogenetics as a measure of chromosomal heterogeneity in primary breast cancer [Abstract]. Cytometry 5: 95, 1991

    Google Scholar 

  25. Waldman FM, Chew K, Ljung B-M, Goodson W, Hom J, Duarte L, Smith HS, Mayall B: A comparison between bromodeoxyuridine and3H thymidine labeling in human breast tumors. Mod Pathol 4: 718–722, 1991

    PubMed  Google Scholar 

  26. Zarbo RJ, Visscher DW, Crissman JD: Two color multiparametric method for flow cytometric DNA analysis of carcinomas using staining for cytokeratin and leukocyte common antigen. Anal Quant Cytol Histol 11: 391, 1989

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Departments of Pathology, Henry Ford Hospital and Harper Hospital, Detroit, Michigan

    D. W. Visscher, S. Wykes, J. Kubus & J. D. Crissman

Authors
  1. D. W. Visscher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Wykes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Kubus
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. D. Crissman
    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

Visscher, D.W., Wykes, S., Kubus, J. et al. Comparison of PCNA/cyclin immunohistochemistry with flow cytometric S-phase fraction in breast cancer. Breast Cancer Res Tr 22, 111–118 (1992). https://doi.org/10.1007/BF01833340

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01833340

Key words

Search

Navigation