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Proliferationsbestimmung beim Mammakarzinom durch den immunhistochemischen Nachweis von Ki-67

Determination of proliferation in breast cancer by immunohistochemical detection of Ki-67

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Zusammenfassung

Genexpressionsprofile haben gezeigt, dass proliferationsassoziiert exprimierte Gene von ausschlaggebender prognostischer Bedeutung beim Mammakarzinom sind. Mit dem immunhistochemischen Marker Ki-67 steht ein routinemäßig in der Pathologie einsetzbares Instrument zur Proliferationsbestimmung zur Verfügung. In zahlreichen retrospektiven aber nur sehr wenigen prospektiven Studien konnte die prognostische Relevanz von Ki-67 gezeigt werden. Trotz hinsichtlich Feldauswahl, Zellzahl, quantitativer oder semiquantitativer Zählweise und Grenzwerten noch nicht vereinheitlichter Bestimmungsmethodik findet Ki-67 eine breite Anwendung in der Mammapathologie. Gründe hierfür sind die im sehr hohen und niedrigen Bereich gute Reproduzierbarkeit, die mögliche Objektivierung des Gradings und die insbesondere an Stanzbiopsien bessere Praktikabilität im Vergleich zum Mitosenzählen. In der neoadjuvanten Therapie des hormonrezeptorpositiven Mammakarzinoms kann Ki-67 wahrscheinlich die Prädiktion der Wirksamkeit einer alleinigen Rezeptorblockade ohne Chemotherapie ermöglichen.

Abstract

Gene expression profiling has demonstrated the prognostic relevance of genes associated with proliferation in breast cancer. The immunohistochemical marker Ki-67 enables routine assessment of proliferation activity in pathology. In a number of retrospective but only few prospective studies the prognostic relevance of Ki-67 in breast cancer could be shown. Although there is no standardized approach with regard to which area of a histological section and how many cells should be counted in a quantitative or semiquantitative fashion as well as to the threshold, Ki-67 is broadly applied in breast pathology. This can be explained by the good reproducibility of the degree of proliferation assessed by Ki-67, at least in the low and high ranges, the possibility to substantiate grading and better practicability in core biopsies in comparison to mitotic counting. In neoadjuvant therapy of hormone receptor positive breast cancer, Ki-67 can probably predict the efficacy of pure hormone receptor blockade without chemotherapy.

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Literatur

  1. Boege F, Andersen A, Jensen S et al (1995) Proliferation-associated nuclear antigen Ki-S1 is identical with topoisomerase II alpha. Delineation of a carboxy-terminal epitope with peptide antibodies. Am J Pathol 146(6):1302–1308

    CAS  PubMed  Google Scholar 

  2. Cheang MC, Chia SK, Voduc D et al (2009) Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 101:736–750

    Article  CAS  PubMed  Google Scholar 

  3. Da Silva L, Clarke C, Lakhani SR (2007) Demystifying basal-like breast carcinomas. J Clin Pathol 60:1328–1332

    Google Scholar 

  4. Denkert C, Loibl S, Müller BM et al (2013) Ki67 levels as predictive and prognostic parameters in pretherapeutic breast cancer core biopsies: a translational investigation in the neoadjuvant GeparTrio trial. Ann Oncol [Epub ahead of print]

  5. De Azambuja E, Cardoso F, Castro G de et al (2007) Ki67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer 96:1504–1513

    Article  Google Scholar 

  6. Dowsett M, Nielsen TO, A’Hern R et al (2011) Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in breast cancer working group. J Natl Cancer Inst 103:1656–1664

    Article  CAS  PubMed  Google Scholar 

  7. Frierson HF Jr, Wolber RA, Berean KW et al (1995) Interobserver reproducibility of the Nottingham modification of the Bloom and Richardson histologic grading scheme for infiltrating ductal carcinoma. Am J Clin Pathol 103:195–198

    PubMed  Google Scholar 

  8. Gerdes J, Lemke H, Baisch H et al (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133(4):1710–1715

    CAS  PubMed  Google Scholar 

  9. Goldhirsch A, Ingle JN, Gelber RD et al (2009) Panel members. Thresholds for therapies: highlights of the St. Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann Oncol 20:1319–1329

    Article  CAS  PubMed  Google Scholar 

  10. Goldhirsch A, Wood WC, Coates AS et al (2011) Strategies for subtypes – dealing with the diversity of breast cancer: highlights of the St. Gallen international expert consensus on the primary therapy of early breast cancer 2011. Ann Oncol 22:1736–1747

    Article  CAS  PubMed  Google Scholar 

  11. Goldhirsch A, Winer EP, Coates AS et al (2013) Personalizing the treatment of women with early breast cancer: highlights of the St. Gallen international expert consensus on the primary therapy of early breast cancer. Ann Oncol 24:2206–2223

    Article  CAS  PubMed  Google Scholar 

  12. Gusterson B (2009) Do ‚basal-like‘ breast cancers really exist? Nat Rev Cancer 9:128–134

    Article  CAS  PubMed  Google Scholar 

  13. Hall PA, McKee PH, Menage HD et al (1993) High levels of p53 protein in UV-irradiated normal human skin. Oncogene 8(1):203–207

    CAS  PubMed  Google Scholar 

  14. Jones RL, Salter J, A’Hern R et al (2009) The prognostic significance of Ki67 before and after neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat 116:53–68

    Article  CAS  PubMed  Google Scholar 

  15. Kwok TC, Rakha EA, Lee AH et al (2010) Histological grading of breast cancer on needle core biopsy: the role of immunohistochemical assessment of proliferation. Histopathology 57:212–219

    Article  PubMed Central  PubMed  Google Scholar 

  16. Kreienberg R, Kopp I, Albert U et al (2012) Interdisziplinäre S-3 Leitlinie für die Diagnostik, Therapie und Nachsorge des Mammakarzinoms. Zuckschwerdt, München

  17. Lehr HA, Hansen DA, Kussick S et al (1999) Assessment of proliferative activity in breast cancer: MIB-1 immunohistochemistry versus mitotic figure count. Hum Pathol 30(11):1314–1320

    Article  CAS  PubMed  Google Scholar 

  18. Ließem S, Fisseler-Eckhoff A, Rüschoff J, Kreipe (2014) Ringversuche zur Qualitätssicherung beim Mammakarzinom. Pathologe, im Druck

  19. Loi S, Haibe-Kains B, Desmedt C et al (2007) Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade. J Clin Oncol 25:1239–1246

    Article  CAS  PubMed  Google Scholar 

  20. Mengel M, Wasielewski R von, Wiese B et al (2002) Inter-laboratory and inter-observer reproducibility of immunohistochemical assessment of the Ki-67 labelling index in a large multi-centre trial. J Pathol 198:292–299

    Article  PubMed  Google Scholar 

  21. Minckwitz von G, Sinn HP, Raab G et al (2008) Clinical response after two cycles compared to HER2, Ki-67, p53, and bcl-2 in independently predicting a pathological complete response after preoperative chemotherapy in patients with operable carcinoma of the breast. Breast Cancer Res 10:R30

    Article  Google Scholar 

  22. O’Shea AM, Rakha EA, Hodi Z et al (2011) Histological grade of invasive carcinoma of the breast assessed on needle core biopsy – modifications to mitotic count assessment to improve agreement with surgical specimens. Histopathology 59:543–548

    Article  Google Scholar 

  23. Penault-Llorca F, André F, Sagan C et al (2009) Ki67 expression and docetaxel efficacy in patients with estrogen receptor-positive breast cancer. J Clin Oncol 27:2809–2815

    Article  CAS  PubMed  Google Scholar 

  24. Perou CM, Sørlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752

    Article  CAS  PubMed  Google Scholar 

  25. Prat A, Cheang MC, Martin M et al (2012) Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal a breast cancer. J Clin Oncol 31:203–209

    Article  PubMed  Google Scholar 

  26. Scharl A (Hrsg) (2013) Aktuelle Empfehlungen zur Prävention, Diagnostik und Therapie früher und fortgeschrittener Mammakarzinome. Zuckschwerdt, München

  27. Scholzen T, Gerdes J (2000) The Ki-67 protein: from the known and the unknown. J Cell Physiol 182:311–322

    Article  CAS  PubMed  Google Scholar 

  28. Schwab U, Stein H, Gerdes J et al (1982) Production of a monoclonal antibody specific for Hodgkin and Sternberg-Reed cells of Hodgkin’s disease and a subset of normal lymphoid cells. Nature 299(5878):65–67

    Article  CAS  PubMed  Google Scholar 

  29. Sheri A, Dowsett M (2012) Developments in Ki67 and other biomarkers for treatment decision making in breast cancer. Ann Oncol 23(Suppl 10):x219–x227

    Article  PubMed  Google Scholar 

  30. Stuart-Harris R, Caldas C, Pinder SE, Pharoah P (2008) Proliferation markers and survival in early breast cancer: a systematic review and meta-analysis of 85 studies in 32,825 patients. Breast 17:323–334

    Article  CAS  PubMed  Google Scholar 

  31. Tang G, Cuzick J, Costantino JP et al (2011) Risk of recurrence and chemotherapy benefit for patients with node-negative, estrogen receptor-positive breast cancer: recurrence score alone and integrated with pathologic and clinical factors. J Clin Oncol 29:4365–4372

    Article  CAS  PubMed  Google Scholar 

  32. Varga Z, Diebold J, Dommann-Scherrer C et al (2012) How reliable is Ki-67 immunohistochemistry in grade 2 breast carcinomas? A QA study of the Swiss working group of breast and gynekopathologists. PLoS One 7(5):e37379

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Viale G, Giobbie-Hurder A, Regan MM et al (2008) Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: results from Breast International Group Trial 1-98 comparing adjuvant tamoxifen with letrozole. J Clin Oncol 26:5569–5575

    Article  PubMed  Google Scholar 

  34. Viale G, Regan MM, Mastropasqua MG et al (2008) Predictive value of tumor Ki67 expression in two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. J Natl Cancer Inst 100:207–212

    Article  CAS  PubMed  Google Scholar 

  35. Wasielewski von R, Klöpper K, Lück HJ, Kreipe H (2006) Improvement of breast cancer grading in punch biopsies: grading with the Ki-67 marker. Pathologe 27:337–345

    Article  Google Scholar 

  36. Yerushalmi R, Woods R, Ravdin PM et al (2010) Ki67 in breast cancer: prognostic and predictive potential. Lancet Oncol 11:174–183

    Article  CAS  PubMed  Google Scholar 

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Einhaltung ethischer Richtlinien

Interessenkonflikt. H. Kreipe, M. Christgens, W. Winkens geben an, dass kein Interessenkonflikt besteht. Alle angewandten Verfahren stehen im Einklang mit den ethischen Normen der verantwortlichen Kommission für Forschung am Menschen (institutionell und national) und mit der Deklaration von Helsinki von 1975 in der revidierten Fassung von 2008. Alle Patienten wurden erst nach erfolgter Aufklärung und Einwilligung in die Studie eingeschlossen.

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  1. Institut für Pathologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland

    M. Christgen, W. Winkens &  H. Kreipe

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  1. M. Christgen
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  2. W. Winkens
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Correspondence to H. Kreipe.

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Christgen, M., Winkens, W. & Kreipe, H. Proliferationsbestimmung beim Mammakarzinom durch den immunhistochemischen Nachweis von Ki-67. Pathologe 35, 54–60 (2014). https://doi.org/10.1007/s00292-013-1843-5

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  • DOI: https://doi.org/10.1007/s00292-013-1843-5

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