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Proliferating-cell nuclear antigen (PC10) immunolabelling and other proliferation indices as prognostic factors in breast cancer

  • Original Papers
  • Clinical Oncology
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Abstract

Proliferating cell nuclear antigen, PCNA (PC10), immunolabelling was determined in 175 women with breast carcinomas and related to other established prognostic factors: flow-cytometric data, volume-corrected mitotic index, sex steroid receptor content and clinical outcome during the mean follow-up of 9 years. The maximum fraction of PCNA-positive nuclei (PCNAmax), the average fraction of positive nuclei (PCNAtot) and the number of intensely stained nuclei per microscope field (PCNAcount) were significantly related to histological grade (P<0.001), DNA ploidy ((P<0.001), S-phase fraction (P<0.001), mitotic index (P<0.001) and sex steroid receptor content (P=0.002). PCNAmax (P=0.015) predicted survival in univariate analysis; PCNAtot (P=0.025), PCNAmax (P=0.007) and PCNAcount (P=0.019) predicted the recurrence-free survival. In axillary-lymph-node-negative tumours, PCNAtot (P=0.092), PCNAmax (P=0.036) and PCNAcount (P=0.006) predicted survival and recurrence-free survival (P=0.011), (P=0.012) and (P=0.006) respectively. In multivariate analysis including clinical, histological, flow-cytometric and biochemical variables, PCNAtot (P=0.004) predicted the recurrence-free survival independently. In axillary-lymph-node-negative breast cancers, PCNAtot predicted accurately the patient survival (P=0.002) and the recurrence-free survival (P=0.002). The results indicate that PCNA immunolabelling has independent prognostic value particularly in local breast cancer.

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Abbreviations

PCNA:

proliferating-cell nuclear antigen

References

  • Aaltomaa S, Lipponen P, Eskelinen M, Kosma V-M, Marin S, Alhava E, Syrjänen K (1991 a) Prognostic scores combining clinical, histological and morphometric variables in assessment of the disease outcome in female breast cancer. Int J Cancer 49:886–892

    PubMed  Google Scholar 

  • Aaltomaa S, Lipponen P, Eskelinen M, Kosma V-M, Marin S, Alhava E, Syrjänen K (1991 b) Hormone receptors as prognostic factors in female breast cancer. Ann Med 23:643–648

    PubMed  Google Scholar 

  • Allegranza A, Girlando S, Arrigoni GL, Veronese S, Mauri FA, Gumbacorta M, Pollo P, DallaPalma P, Barbarechi M (1991) Proliferating cell nuclear antigen expression in central nervous system neoplasms. Virchows Archiv [A] 419:417–423

    Google Scholar 

  • Bloom HJG, Richardson WW (1957) Histological grading and prognosis in breast cancer. Br J Cancer 11:359–377

    PubMed  Google Scholar 

  • Bravo R, Frank R, Blindell PA, Macdonald-Bravo H (1987) Cyclin/PCNA is the axillary protein to DNA polymerase-delta. Nature 326:515–520

    PubMed  Google Scholar 

  • Cox DR (1972) Regression models and life tables with discussion. J R Statist Soc [B] 34:187–192

    Google Scholar 

  • Diest PJ van, Baak JPA (1991) The morphometric prognostic index is the strongest prognosticator in premenopausal lymph node-negative and lymph node-positive breast cancer patients. Hum Pathol 22:326–330

    PubMed  Google Scholar 

  • Hall PA, Levison DA, Woods AL, Yu CC-W, Kellock DB, Watkins JA, Barnes DM, Gillet CE, Camplejohn R, Dover R, Waseem NH, Lane DP (1990) Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms. J Pathol 162:285–294

    PubMed  Google Scholar 

  • Haneda H, Katabami M, Miyamoto H, Isobe H, Shimizu T, Ishiguro A, Moriuti T, Takasaki Y, Kawakami Y (1991) The relationship of the proliferating cell nuclear antigen protein tocis-diammine-dichloroplatinum(II) resistance of a murine leukemia cell line P388/CDDP. Oncology 48:234–238

    PubMed  Google Scholar 

  • Helin HJ, Helle MJ, Kallioniemi O-P, Isola JJ (1989) Immunohistochemical determination of estrogen and progesterone receptors in human breast carcinoma. Correlation with histopathology and DNA flow cytometry. Cancer 63:1761–1767

    PubMed  Google Scholar 

  • Jagoe R, Steel JH, Vucicevic V, Alexander N, Noorden S van, Wootton R, Polak JM (1991) Observer variation in quantification of immunohistochemistry by image analysis. Histochem J 23:541–547

    PubMed  Google Scholar 

  • Jaskulski D, deRiel JK, Mercher WE, Calabretta B, Baserga R (1988) Inhibition of cellular proliferation by antisense oligodeoxynucleotides to PCNA cyclin. Science 240:1544–1546

    PubMed  Google Scholar 

  • Kamel OW, LeBrun DP, Davis RE, Berry GJ, Warnke RA (1991) Growth fraction estimation of malignant lymphomas in formalin-fixed paraffin-embedded tissue using anti-PCNA/cyclin 19A2. Am J Pathol 138:1471–1477

    PubMed  Google Scholar 

  • Kamerow HN, Perchick A, Burstein DE (1991) Immunocytochemical detection of cyclin, a proliferation associated protein in cytologic preparations. Acta Cytol 35:491–496

    PubMed  Google Scholar 

  • Lawry J, Giri D, Rogers K, Duncan JL (1990) The value of assessing cell proliferation in breast cancer. J Microsc 159:265–275

    PubMed  Google Scholar 

  • Lee E, Desu M (1972) A computer program for comparing k samples with right censored data. Comput Programs Biomed 2:315–318

    PubMed  Google Scholar 

  • Leonardi E, Girlando S, Serio G, Mauri FA, Perrone G, Scampini S, Dalla Palma P, Barbareschi M (1992) PCNA and Ki67 expression in breast carcinoma: Correlations with clinical and biological variables. J Clin Pathol 45:416–419

    PubMed  Google Scholar 

  • Lipponen PK, Eskelinen MJ (1992) Cell proliferation of transitional cell bladder tumours determined by PCNA/cyclin immunostaining and its prognostic value. Br J Cancer 66:171–176

    PubMed  Google Scholar 

  • Lipponen P, Aaltomaa S, Eskelinen M, Papinaho S, Klemi P, Kosma V-M, Marin S, Syrjänen K (1992) Sex steroid receptors, S-phase fraction and DNA ploidy as determinants of the risk of relapse and death of female breast cancer. Anticancer Res 12:677–682

    PubMed  Google Scholar 

  • Mathiesen O, Bonderup J, Carl J, Panduro J, Pedersen KO (1991) The prognostic value of estrogen and progesterone receptors in female breast cancer. Acta Oncol 30:691–695

    PubMed  Google Scholar 

  • Mercer WE, Shields MT, Lin D, Appella E, Ullrich SJ (1991) Growth suppression by wild-type p53 protein is accompanied by selective down regulation of proliferating cell nuclear antigen expression. Proc Natl Acad Sci USA 88:1958–1962

    PubMed  Google Scholar 

  • Miyachi K, Fritzler MJ, Tan EM (1978) Autoantibody to nuclear antigen in proliferating cells. J Immunol 121:2228–2234

    PubMed  Google Scholar 

  • Morris GF, Mathews MB (1989) Regulation of proliferating cell nuclear antigen during the cell cycle. J Biol Chem 264:13856–13864

    PubMed  Google Scholar 

  • Scott JR, Hall PA, Haldane JS, Noorden S van, Price Y, Lane DP, Wright NA (1991) A comparison of immunohistochemical markers of cell proliferation with experimentally determined growth fraction. J Pathol 165:173–178

    PubMed  Google Scholar 

  • Uyterlinde AM, Baak JPA, Schipper NW, Peterse H, Matze E, Meijer CJ (1990) Further evaluation of the prognostic value of morphometric and flow cytometric parameters in breast cancer patients with long follow-up. Int J Cancer 45:1–7

    Google Scholar 

  • Vihko R, Jänne O, Kontula K, Syrjälä P (1980) Female sex steroid receptor status in primary and metastatic breast carcinoma and its relationship to serum steroid and peptide hormone levels. Int J Cancer 26:12–31

    Google Scholar 

  • WHO (1981) Histological typing of breast tumors. International histological classification of tumors 2. WHO, Geneva

    Google Scholar 

  • Woods AL, Hall PA, Shepherd NA, Hanby AM, Waseem NH, Lane DP, Levison DA (1991) The assessment of proliferating cell nuclear antigen (PCNA) immunostaining in primary gastrointestinal lymphomas and its relationship to histological grade, S+G2+M phase fraction (flow cytometric analysis) and prognosis. Histopathology 19:21–27

    PubMed  Google Scholar 

  • Yu C-W, Hall PA, Fletcher CMD, Champlejohn RS, Waseem NH, Lane DP, Levison DA (1991) Hemangiopericytomas: the prognostic value of immunohistochemical staining with a monoclonal antibody to proliferating cell nuclear antigen (PCNA). Histopathology 19:29–33

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, University of Kuopio, SF-70210, Kuopio, Finland

    S. Aaltomaa

  2. Department of Pathology, University of Kuopio, Finland

    P. Lipponen, S. Papinaho & K. Syrjänen

  3. A.I. Virtanen Institute, University of Kuopio, Finland

    K. Syrjänen

Authors
  1. S. Aaltomaa
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  2. P. Lipponen
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  3. S. Papinaho
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  4. K. Syrjänen
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Aaltomaa, S., Lipponen, P., Papinaho, S. et al. Proliferating-cell nuclear antigen (PC10) immunolabelling and other proliferation indices as prognostic factors in breast cancer. J Cancer Res Clin Oncol 119, 288–294 (1993). https://doi.org/10.1007/BF01212727

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  • DOI: https://doi.org/10.1007/BF01212727

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