title: Interobserver agreement of proliferation index (Ki-67) outperforms mitotic count in pulmonary carcinoids.
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.
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany. arne.warth@med.uni-heidelberg.de
authors.forename: Arne
authors.initials: A
authors.lastname: Warth
authors.forename: Ludger
authors.initials: L
authors.lastname: Fink
authors.forename: Annette
authors.initials: A
authors.lastname: Fisseler-Eckhoff
authors.forename: Danny
authors.initials: D
authors.lastname: Jonigk
authors.forename: Marius
authors.initials: M
authors.lastname: Keller
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: Ralf J
authors.initials: RJ
authors.lastname: Rieker
authors.forename: Peter
authors.initials: P
authors.lastname: Sinn
authors.forename: Stephan
authors.initials: S
authors.lastname: Söder
authors.forename: Alex
authors.initials: A
authors.lastname: Soltermann
authors.forename: Klaus
authors.initials: K
authors.lastname: Willenbrock
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis*; D002276:Carcinoid Tumor / Q000453:epidemiology / Q000473:pathology*; D049109:Cell Proliferation; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D019394:Ki-67 Antigen / Q000032:analysis*; D008175:Lung Neoplasms / Q000453:epidemiology / Q000473:pathology*; D008940:Mitotic Index; D060787:Neoplasm Grading / Q000379:methods*; D015588:Observer Variation
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen
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