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. 1998 Aug;78(4):460–465. doi: 10.1038/bjc.1998.515

MIB-1 labelling index is an independent prognostic marker in primary breast cancer.

R L Jansen 1, P S Hupperets 1, J W Arends 1, S R Joosten-Achjanie 1, A Volovics 1, H C Schouten 1, H F Hillen 1
PMCID: PMC2063089  PMID: 9716027

Abstract

The proliferative activity of a tumour is considered to be an important prognostic factor in primary breast cancer. We have investigated the prognostic value of the MIB-1 labelling index in 341 patients with primary breast cancer and compared the results with the S-phase fraction in 220 patients of the same cohort. All patients were treated in one hospital and had a median follow-up of 128 months. No correlation between MIB-1 labelling and S-phase fraction could be demonstrated. MIB-1 had prognostic value for disease-free survival in the whole group of patients (P < 0.001) and in the node-negative subgroup (P < 0.001). In multivariate analysis, MIB-1 was an independent prognostic factor (P = 0.004) besides axillary lymph node status (P = 0.001). In univariate analysis high S-phase fraction was associated with decreased overall survival (P = 0.04); however, not in multivariate analysis. Moreover, S-phase fraction had a borderline prognostic significance for post-relapse survival in multivariate analysis (P= 0.08). Thus, in conclusion, the growth fraction of a tumour as determined by the MIB-1 labelling index is an important prognostic factor in patients with primary breast cancer.

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Selected References

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  1. Bouzubar N., Walker K. J., Griffiths K., Ellis I. O., Elston C. W., Robertson J. F., Blamey R. W., Nicholson R. I. Ki67 immunostaining in primary breast cancer: pathological and clinical associations. Br J Cancer. 1989 Jun;59(6):943–947. doi: 10.1038/bjc.1989.200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brown R. W., Allred C. D., Clark G. M., Osborne C. K., Hilsenbeck S. G. Prognostic value of Ki-67 compared to S-phase fraction in axillary node-negative breast cancer. Clin Cancer Res. 1996 Mar;2(3):585–592. [PubMed] [Google Scholar]
  3. Clayton F. Pathologic correlates of survival in 378 lymph node-negative infiltrating ductal breast carcinomas. Mitotic count is the best single predictor. Cancer. 1991 Sep 15;68(6):1309–1317. doi: 10.1002/1097-0142(19910915)68:6<1309::aid-cncr2820680621>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  4. Dettmar P., Harbeck N., Thomssen C., Pache L., Ziffer P., Fizi K., Jänicke F., Nathrath W., Schmitt M., Graeff H. Prognostic impact of proliferation-associated factors MIB1 (Ki-67) and S-phase in node-negative breast cancer. Br J Cancer. 1997;75(10):1525–1533. doi: 10.1038/bjc.1997.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Domagala W., Markiewski M., Harezga B., Dukowicz A., Osborn M. Prognostic significance of tumor cell proliferation rate as determined by the MIB-1 antibody in breast carcinoma: its relationship with vimentin and p53 protein. Clin Cancer Res. 1996 Jan;2(1):147–154. [PubMed] [Google Scholar]
  6. Fentiman I. S., Epstein R., Barr L. Is routine axillary nodal dissection necessary in the treatment of breast cancer? Eur J Cancer. 1996 Aug;32A(9):1460–1463. doi: 10.1016/0959-8049(95)00656-7. [DOI] [PubMed] [Google Scholar]
  7. 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. 1994 Jun 15;57(6):822–829. doi: 10.1002/ijc.2910570610. [DOI] [PubMed] [Google Scholar]
  8. Gerdes J., Becker M. H., Key G., Cattoretti G. Immunohistological detection of tumour growth fraction (Ki-67 antigen) in formalin-fixed and routinely processed tissues. J Pathol. 1992 Sep;168(1):85–86. doi: 10.1002/path.1711680114. [DOI] [PubMed] [Google Scholar]
  9. Hedley D. W., Clark G. M., Cornelisse C. J., Killander D., Kute T., Merkel D. DNA Cytometry Consensus Conference. Consensus review of the clinical utility of DNA cytometry in carcinoma of the breast. Breast Cancer Res Treat. 1993 Oct;28(1):55–59. doi: 10.1007/BF00666357. [DOI] [PubMed] [Google Scholar]
  10. Hedley D. W. Flow cytometry using paraffin-embedded tissue: five years on. Cytometry. 1989 May;10(3):229–241. doi: 10.1002/cyto.990100302. [DOI] [PubMed] [Google Scholar]
  11. Hiddemann W., Schumann J., Andreef M., Barlogie B., Herman C. J., Leif R. C., Mayall B. H., Murphy R. F., Sandberg A. A. Convention on nomenclature for DNA cytometry. Committee on Nomenclature, Society for Analytical Cytology. Cancer Genet Cytogenet. 1984 Oct;13(2):181–183. doi: 10.1016/0165-4608(84)90059-1. [DOI] [PubMed] [Google Scholar]
  12. Horiguchi J., Iino Y., Takei H. Expression of pS2 estrogen-inducible protein in primary breast cancer. Oncology. 1996 Jan-Feb;53(1):12–15. doi: 10.1159/000227527. [DOI] [PubMed] [Google Scholar]
  13. Hupperets P. S., Wils J., Volovics L., Schouten L., Fickers M., Bron H., Schouten H. C., Jager J., Smeets J., de Jong J. Adjuvant chemohormonal therapy with cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) with or without medroxyprogesterone acetate for node-positive breast cancer patients. Ann Oncol. 1993 Apr;4(4):295–301. doi: 10.1093/oxfordjournals.annonc.a058485. [DOI] [PubMed] [Google Scholar]
  14. Hupperets P., Wils J., Volovics L., Schouten L., Fickers M., Bron H., Schouten H., Jager J., de Jong J., Beex L. Adjuvant chemo-hormonal therapy with cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) with or without medroxyprogesterone acetate for node-positive cancer patients. Update at 7-year follow-up. Ann Oncol. 1995 Jan;6(1):90–91. doi: 10.1093/oxfordjournals.annonc.a059059. [DOI] [PubMed] [Google Scholar]
  15. Jensen V., Ladekarl M., Holm-Nielsen P., Melsen F., Soerensen F. B. The prognostic value of oncogenic antigen 519 (OA-519) expression and proliferative activity detected by antibody MIB-1 in node-negative breast cancer. J Pathol. 1995 Aug;176(4):343–352. doi: 10.1002/path.1711760405. [DOI] [PubMed] [Google Scholar]
  16. Keshgegian A. A., Cnaan A. Proliferation markers in breast carcinoma. Mitotic figure count, S-phase fraction, proliferating cell nuclear antigen, Ki-67 and MIB-1. Am J Clin Pathol. 1995 Jul;104(1):42–49. doi: 10.1093/ajcp/104.1.42. [DOI] [PubMed] [Google Scholar]
  17. Pietiläinen T., Lipponen P., Aaltomaa S., Eskelinen M., Kosma V. M., Syrjänen K. The important prognostic value of Ki-67 expression as determined by image analysis in breast cancer. J Cancer Res Clin Oncol. 1996;122(11):687–692. doi: 10.1007/BF01209033. [DOI] [PubMed] [Google Scholar]
  18. Pinder S. E., Wencyk P., Sibbering D. M., Bell J. A., Elston C. W., Nicholson R., Robertson J. F., Blamey R. W., Ellis I. O. Assessment of the new proliferation marker MIB1 in breast carcinoma using image analysis: associations with other prognostic factors and survival. Br J Cancer. 1995 Jan;71(1):146–149. doi: 10.1038/bjc.1995.30. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Querzoli P., Albonico G., Ferretti S., Rinaldi R., Magri E., Indelli M., Nenci I. MIB-1 proliferative activity in invasive breast cancer measured by image analysis. J Clin Pathol. 1996 Nov;49(11):926–930. doi: 10.1136/jcp.49.11.926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Railo M., Nordling S., von Boguslawsky K., Leivonen M., Kyllönen L., von Smitten K. Prognostic value of Ki-67 immunolabelling in primary operable breast cancer. Br J Cancer. 1993 Sep;68(3):579–583. doi: 10.1038/bjc.1993.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Remmele W., Mühlfait V., Keul H. G. Estimation of the proliferative activity of human breast cancer tissue by means of the Ki-67 and MIB-1 antibodies--comparative studies on frozen and paraffin sections. Virchows Arch. 1995;426(5):435–439. doi: 10.1007/BF00193164. [DOI] [PubMed] [Google Scholar]
  22. Rudas M., Gnant M. F., Mittlböck M., Neumayer R., Kummer A., Jakesz R., Reiner G., Reiner A. Thymidine labeling index and Ki-67 growth fraction in breast cancer: comparison and correlation with prognosis. Breast Cancer Res Treat. 1994;32(2):165–175. doi: 10.1007/BF00665767. [DOI] [PubMed] [Google Scholar]
  23. Schutte B., Reynders M. M., Bosman F. T., Blijham G. H. Flow cytometric determination of DNA ploidy level in nuclei isolated from paraffin-embedded tissue. Cytometry. 1985 Jan;6(1):26–30. doi: 10.1002/cyto.990060106. [DOI] [PubMed] [Google Scholar]
  24. Seshadri R., Leong A. S., McCaul K., Firgaira F. A., Setlur V., Horsfall D. J. Relationship between p53 gene abnormalities and other tumour characteristics in breast-cancer prognosis. Int J Cancer. 1996 Apr 22;69(2):135–141. doi: 10.1002/(SICI)1097-0215(19960422)69:2<135::AID-IJC12>3.0.CO;2-8. [DOI] [PubMed] [Google Scholar]
  25. Shi S. R., Key M. E., Kalra K. L. Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem. 1991 Jun;39(6):741–748. doi: 10.1177/39.6.1709656. [DOI] [PubMed] [Google Scholar]
  26. Silvestrini R., Daidone M. G., Luisi A., Boracchi P., Mezzetti M., Di Fronzo G., Andreola S., Salvadori B., Veronesi U. Biologic and clinicopathologic factors as indicators of specific relapse types in node-negative breast cancer. J Clin Oncol. 1995 Mar;13(3):697–704. doi: 10.1200/JCO.1995.13.3.697. [DOI] [PubMed] [Google Scholar]
  27. Veronese S. M., Gambacorta M., Gottardi O., Scanzi F., Ferrari M., Lampertico P. Proliferation index as a prognostic marker in breast cancer. Cancer. 1993 Jun 15;71(12):3926–3931. doi: 10.1002/1097-0142(19930615)71:12<3926::aid-cncr2820711221>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  28. Weikel W., Beck T., Mitze M., Knapstein P. G. Immunohistochemical evaluation of growth fractions in human breast cancers using monoclonal antibody Ki-67. Breast Cancer Res Treat. 1991 Aug;18(3):149–154. doi: 10.1007/BF01990030. [DOI] [PubMed] [Google Scholar]
  29. van Diest P. J., Baak J. P., Matze-Cok P., Wisse-Brekelmans E. C., van Galen C. M., Kurver P. H., Bellot S. M., Fijnheer J., van Gorp L. H., Kwee W. S. Reproducibility of mitosis counting in 2,469 breast cancer specimens: results from the Multicenter Morphometric Mammary Carcinoma Project. Hum Pathol. 1992 Jun;23(6):603–607. doi: 10.1016/0046-8177(92)90313-r. [DOI] [PubMed] [Google Scholar]

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