Journal Article
. 2002 Oct; 198(3):292-9.
doi: 10.1002/path.1218.

Inter-laboratory and inter-observer reproducibility of immunohistochemical assessment of the Ki-67 labelling index in a large multi-centre trial

Michael Mengel 1 Reinhard von Wasielewski  Birgitt Wiese  Thomas Rüdiger  Hans Konrad Müller-Hermelink  Hans Kreipe  
  • PMID: 12375261
  •     59 citations


Proliferative activity of tumour cells, as assessed by the Ki-67 labelling index, has been suggested as a potential prognostic indicator in many neoplastic diseases. Meaningful application of the immunohistochemically determined tumour cell growth fraction in clinical decision-making requires information about its inter-laboratory reproducibility. To assess the reproducibility of Ki-67 determined growth fraction, a multi-centre immunohistochemical trial was performed with 172 participating laboratories, each testing 30 different tissue samples. Evaluating 5160 Ki-67 labelling indices with a newly developed tissue microarray, good inter-observer reproducibility but high inter-laboratory variability was found. Reassessment of all stainings revealed considerable inter-laboratory differences in the intensity and frequency of labelled nuclei, suggesting that antigen retrieval or staining techniques are predominantly responsible for the inter-laboratory variability found in this trial. Consequently, cut-off levels for Ki-67, suggested to distinguish prognostic subgroups in tumours, appear to have limited reproducibility in a multi-centre approach. It is concluded that there is a need to standardize the immunohistochemical determination of the Ki-67 labelling index when it is used as a prognostic indicator in surgical pathology.

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