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Interobserver agreement of proliferation index (Ki-67) outperforms mitotic count in pulmonary carcinoids

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Abstract

Evaluation of proliferative activity is a cornerstone in the classification of endocrine tumors; in pulmonary carcinoids, the mitotic count delineates typical carcinoid (TC) from atypical carcinoid (AC). Data on the reproducibility of manual mitotic counting and other methods of proliferation index evaluation in this tumor entity are sparse. Nine experienced pulmonary pathologists evaluated 20 carcinoid tumors for mitotic count (hematoxylin and eosin) and Ki-67 index. In addition, Ki-67 index was automatically evaluated with a software-based algorithm. Results were compared with respect to correlation coefficients (CC) and kappa values for clinically relevant grouping algorithms. Evaluation of mitotic activity resulted in a low interobserver agreement with a median CC of 0.196 and a median kappa of 0.213 for the delineation of TC from AC. The median CC for hotspot (0.658) and overall (0.746) Ki-67 evaluation was considerably higher. However, kappa values for grouped comparisons of overall Ki-67 were only fair (median 0.323). The agreement of manual and automated Ki-67 evaluation was good (median CC 0.851, median kappa 0.805) and was further increased when more than one participant evaluated a given case. Ki-67 staining clearly outperforms mitotic count with respect to interobserver agreement in pulmonary carcinoids, with the latter having an unacceptable low performance status. Manual evaluation of Ki-67 is reliable, and consistency further increases with more than one evaluator per case. Although the prognostic value needs further validation, Ki-67 might perspectively be considered a helpful diagnostic parameter to optimize the separation of TC from AC.

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Acknowledgments

Iver Petersen, Philipp A. Schnabel, Klaus Junker, Alicia Morresi-Hauf, and Florian Länger are acknowledged for their valuable discussions.

Conflict of interest

None.

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Authors and Affiliations

  1. Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany

    Arne Warth, Marius Keller, Peter Sinn & Wilko Weichert

  2. Institute of Pathology and Cytology, Wetzlar, Germany

    Ludger Fink

  3. Institute of Pathology and Cytology, Horst-Schmidt Hospital, Wiesbaden, Germany

    Annette Fisseler-Eckhoff & Klaus Willenbrock

  4. Institute for Pathology, University Hospital Hannover, Hannover, Germany

    Danny Jonigk

  5. Department of Clinical Pathology, Robert-Bosch Hospital and Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology, Stuttgart, Germany

    German Ott

  6. Institute for Pathology, University Hospital Erlangen-Nürnberg, Erlangen, Germany

    Ralf J. Rieker & Stephan Söder

  7. Institute of Surgical Pathology, University Hospital Zürich, Zürich, Switzerland

    Alex Soltermann

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  1. Arne Warth
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  2. Ludger Fink
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on behalf of the Pulmonary Pathology Working Group of the German Society of Pathology

Corresponding author

Correspondence to Arne Warth.

Electronic supplementary material

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Supplementary Figure 1

Distribution of mitotic counts for all observers and all evaluated cases. (PPT 114 kb)

Supplementary Figure 2

Distribution of overall Ki-67 count for all observers and all evaluated cases. Automated evaluation is given as a reference on the right hand side of each case (red bar). (PPT 115 kb)

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Warth, A., Fink, L., Fisseler-Eckhoff, A. et al. Interobserver agreement of proliferation index (Ki-67) outperforms mitotic count in pulmonary carcinoids. Virchows Arch 462, 507–513 (2013). https://doi.org/10.1007/s00428-013-1408-2

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  • DOI: https://doi.org/10.1007/s00428-013-1408-2

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