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Lack of prognostic significance of the monoclonal antibody Ki-S1, a novel marker of proliferative activity, in node-negative breast carcinoma

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Abstract

In a series of 205 node-negative breast cancers (NNBC), we determined staining by the novel antibody Ki-S1, a marker of tumor cell proliferation, in order to test its association with other prognostic variables and its prognostic significance. Ki-S1 was determined in routinely formalin-fixed paraffin-embedded tumor samples. Ki-S1 gave a nuclear staining in the majority of the carcinomas (188 of 205), with percentages of reacting nuclei ranging from 2% to 90% (median value of 7%). In 107 tumors frozen sections were available to also assess the Ki-67 antibody. Among these, 94 had a nuclear staining of cancer cells ranging from 5% to 80% (median value of 7%). In 46 tumors we also determined the MIB-1 antibody. The percentage of MIB-1 nuclear staining ranged from 1% to 50% (median value of 20%). There was no significant relationship between Ki-S1 and the other two cell kinetic markers. Ki-S1 labeling was significantly associated only with tumor size (p = 0.03).

With a median follow-up of 6 years, Ki-S1 had no significant prognostic value for either relapse-free survival (RFS) or overall survival (OS)(Ki-S1 as continuous logarithmic variable; p = 0.86 and p = 0.23, respectively). For RFS the following variables had a significant prognostic value: Ki-67 (≤ 10% vs > 10%; p = 0.037); progesterone receptor (PgR) expression (− vs +/++; p = 0.041); tumor size (pT1 vs pT2−3; p = 0.042) and grading (GI vs GII−III; p = 0.047). For OS, tumor size (p = 0.0044), age (continuous variable; p = 0.0060), and Ki-67 (p = 0.043) were significantly prognostic.

In multivariate analysis (final model), only tumor size retained a significant and independent prognostic value for RFS (p = 0.0042). For OS, both tumor size (p = 0.0029) and age (≤ 55 years vs > 55 years; p = 0.041) retained significance in the multivariate model.

In conclusion, Ki-S1 does not seem to have prognostic relevance in this series of NNBC. Possible hypotheses to explain this observation are discussed.

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References

  1. Silvestrini R, Daidone MG, Gasparini G: Cell kinetics as a prognostic marker in node-negative breast cancer. Cancer 56: 1981–1987, 1985

    Google Scholar 

  2. Tubiana M, Pejovic MH, Chavaudra G, Contesso G, Malaise EP: The long-term prognosis significance of the thymidine labeling index in breast cancer. Int J Cancer 33: 441–445, 1984

    PubMed  Google Scholar 

  3. 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 

  4. Stal O, Dufmats M, Hatschek T, Carstensen J, Klintenberg C, Rutquist LE, Skoog L, Sullivan S, Wingren S, Nordenskjold B: S-phase fraction is a prognostic factor in stage I breast carcinoma. J Clin Oncol 11: 1717–1722, 1993

    PubMed  Google Scholar 

  5. Gasparini G, Boracchi P, Verderio P, Bevilacqua P: Cell kinetics in human breast cancer: Comparison between the prognostic value of the cytofluorimetric S-phase fraction and that of the antibodies to Ki-67 and PCNA antigens detected by immunocytochemistry. Int J Cancer 57: 822–829, 1994

    PubMed  Google Scholar 

  6. Miller WR: Prognostic factors in breast cancer (Editorial). Br J Cancer 66: 775–776, 1992

    PubMed  Google Scholar 

  7. Hall PA, Woods A: Immunohistochemical markers of cell proliferation. Achievements, problems and prospects. Cell Tissue Kinet 23: 531–549, 1990

    Google Scholar 

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

    PubMed  Google Scholar 

  9. Key G, Becker MHG, Baron B, Duchrow M, Schluter C, Flad HD, Gerdes J: New Ki-67 equivalent murine monoclonal antibodies (MIB 1–3) generated against bacterially expressed parts of the Ki-67 cDNA containing three 62 bp repetitive elements encoding for the Ki-67 epitope. Lab Invest 68: 629–636, 1993

    PubMed  Google Scholar 

  10. Waseem NH, Lane DP: Monoclonal-antibody analysis of the proliferating nuclear antigen (PCNA). Structural conservation and the detection of a nuclear form. J Cell Sci 96: 121–129, 1990

    PubMed  Google Scholar 

  11. Kreipe H, Heidebrecht HJ, Hansen S, Rohlk S, Wacker HH, Tiemann M, Radzun HJ, Parwaresch MR: A new proliferation associated nuclear antigen detectable in paraffin-embedded tissues by the monoclonal antibody Ki-S1. Am J Pathol 142: 3–10, 1993

    PubMed  Google Scholar 

  12. McCormick D, Yu C, Hobbs C, Hall PA: The relevance of antibody concentration to the immunohistological quantification of cell proliferation-associated antigens. Histopathology 22: 543–547, 1993

    PubMed  Google Scholar 

  13. Camplejohn RS, Brock A, Barnes DM, Gillet C, Raikundalia B, Kreipe H, Parwaresch MR: Ki-S1, a novel proliferative marker: flow cytometric assessment of staining in human breast carcinoma cells. Br J Cancer 67: 657–662, 1993

    PubMed  Google Scholar 

  14. Gillett CE, Barnes DM, Camplejohn RS: A comparison of three cell cycle associated antigens as markers of proliferative activity and prognosis in breast carcinoma. J Clin Pathol 46: 1126–1128, 1993

    PubMed  Google Scholar 

  15. Kreipe H, Alm P, Olsson H, Hauberg M, Fisher L, Parwaresch R: Prognostic significance of a formalin-resistant nuclear proliferation antigen in mammary carcinomas as determined by the monoclonal antibody Ki-S1. Am J Pathol 142: 651–657, 1993

    PubMed  Google Scholar 

  16. Sampson SA, Kreipe H, Gillett CE, Smith CE, Smith P Chaudary MA, Khan A, Wicks K, Parwaresch MR, Barnes DM: Ki-S1 a novel monoclonal antibody which recognizes proliferating cells: evaluation of its relationship to prognosis in mammary carcinoma. J Pathol 168: 179–185, 1992

    PubMed  Google Scholar 

  17. Veronesi U, Saccozzi R, Del Vecchio M, Banfi A, Clemente C, De Lena M, Gallus G, Greco M, Luini A, Marubini E, Muscolino G, Rilke F, Salvadori B, Zecchini A, Zucali R: Comparing radical mastectomy with quadrantectomy, axillary dissection and radiotherapy in patients with small cancers of the breast. N Engl J Med 305: 6–11, 1981

    PubMed  Google Scholar 

  18. Fisher ER, Gregorio RM, Fisher B: The pathology of invasive breast cancer. A syllabus derived from findings of the National Surgical Adjuvant Breast Project (protocol n° 4). Cancer 36: 1–85, 1975

    PubMed  Google Scholar 

  19. Bloom HG, Richardson WW: Histological grading and prognosis. Br J Cancer 11: 359–377, 1957

    PubMed  Google Scholar 

  20. Gasparini G, Pozza F, Bevilacqua P, Meli S, Boracchi P, Reitano M, Santini G, Marubini E, Sainsbury JRC: Growth fraction (Ki-67 antibody) determination in early-stage breast carcinoma: histologic, clinical and prognostic correlations. Breast 1: 92–99, 1992

    Google Scholar 

  21. Cattoretti G, Becker MHG, Key G, Gerdes J: Molecular antibodies against recombinant parts of the Ki-67 antigen (MIB-1 and MIB-3) detect proliferating cells in microwave-processed formalin-fixed paraffin sections. J Pathol 168: 357–363, 1992

    PubMed  Google Scholar 

  22. Barbareschi M, Girlando S, Mauri FM, Forti S, Eccher C, Mauri FA, Togni R, Dalla Palma P, Doglioni C: Quantitative growth fraction evaluation with MIB-1 and Ki-67 antibodies in breast carcinomas. Am J Clin Pathol 102: 171–175, 1994

    PubMed  Google Scholar 

  23. Anderson J, Orntoft TF, Poulsen HS: Immunohistochemical demonstration of oestrogen receptors (ER) in formalinfixed paraffin-embedded human breast cancer tissue by use of a monoclonal antibody to ER. J Histochem Cytochem 36: 1553–1560, 1988

    PubMed  Google Scholar 

  24. Bevilacqua P, Pea M, Gasparini G: Immunocytochemical detection of progesterone receptor by monoclonal KD-68 antibody in operable breast cancer: Correlations with biochemical assay, pathological features and cell proliferative rate. Eur J Cancer Clin Oncol 25: 1595–1602, 1989

    PubMed  Google Scholar 

  25. Bland JM, Altman DG: Statistical methods for assessing agreement between two methods of clinical measurement. Lancet i: 307–310, 1986

    Google Scholar 

  26. Gasparini G, Gullick WJ, Bevilacqua P, Sainsbury JRC, Meli S, Boracchi P, Testolin A, La Malfa G, Pozza F: Human breast cancer: Prognostic significance of the c-erbB-2 oncoprotein compared with epidermal growth factor receptor, DNA ploidy, and conventional pathologic features. J Clin Oncol 10: 686–695, 1992

    PubMed  Google Scholar 

  27. Gore SM, Pocock SJ, Kerr GR: Regression models and non-proportional hazards in the analysis of breast cancer survival. Appl Statist 33: 176–195, 1984

    Google Scholar 

  28. Bennet S: Log logistic regression models for survival data. Appl Stat 32: 165–171, 1983

    Google Scholar 

  29. Altman DG, Lausen B, Sauerbrei W, Schumacher M: Danger of using ‘optimal’ cutpoints in the evaluation of prognostic factors. J Natl Cancer Inst 86: 829–835, 1994 (commentary)

    PubMed  Google Scholar 

  30. Lausen B, Schumacher M: Maximally selected rank statistics. Biometrics 48: 78–85, 1992

    Google Scholar 

  31. Rogers S, Wells R, Rechsteiner M: Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science 234: 364–367, 1986

    PubMed  Google Scholar 

  32. Linden MD, Torres FA, Kubus J, Zarbo RJ: Clinical application of morphologic and immunohistochemical assessments of cell proliferation (editorial). Am J Clin Pathol 7 (suppl) S4-S13, 1992

    Google Scholar 

  33. Gasparini G, Pozza F, Harris AL: Evaluating the potential usefulness of new prognostic and predictive indicators in node-negative breast cancer patients (review). J Natl Cancer Inst 85: 1206–1219, 1993

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Oncology, St. Bartolo Regional Medical Centre, 36100, Vicenzo, Italy

    Pierantonio Bevilacqua, Emanuela Bonoldi & Giampietro Gasparini

  2. Institute of Medical Statistics and Biometry, University of Milan, Milan, Italy

    Paolo Verderio & Patrizia Boracchi

  3. St. Chiara Medical Centre, Trento, Italy

    Mattia Barbareschi & Paolo Dalla Palma

Authors
  1. Pierantonio Bevilacqua
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  2. Paolo Verderio
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  3. Mattia Barbareschi
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  4. Emanuela Bonoldi
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  5. Patrizia Boracchi
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  6. Paolo Dalla Palma
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  7. Giampietro Gasparini
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Bevilacqua, P., Verderio, P., Barbareschi, M. et al. Lack of prognostic significance of the monoclonal antibody Ki-S1, a novel marker of proliferative activity, in node-negative breast carcinoma. Breast Cancer Res Tr 37, 123–133 (1996). https://doi.org/10.1007/BF01806494

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