TY - JOUR
T1 - An international Ki67 reproducibility study in adrenal cortical Carcinoma
AU - Papathomas, Thomas G.
AU - Pucci, Eugenio
AU - Giordano, Thomas J.
AU - Lu, Hao
AU - Duregon, Eleonora
AU - Volante, Marco
AU - Papotti, Mauro
AU - Lloyd, Ricardo V.
AU - Tischler, Arthur S.
AU - Van Nederveen, Francien H.
AU - Nose, Vania
AU - Erickson, Lori
AU - Mete, Ozgur
AU - Asa, Sylvia L.
AU - Turchini, John
AU - Gill, Anthony J.
AU - Matias-Guiu, Xavier
AU - Skordilis, Kassiani
AU - Stephenson, Timothy J.
AU - Tissier, Frederique
AU - Feelders, Richard A.
AU - Smid, Marcel
AU - Nigg, Alex
AU - Korpershoek, Esther
AU - Van Der Spek, Peter J.
AU - Dinjens, Winand N.M.
AU - Stubbs, Andrew P.
AU - De Krijger, Ronald R.
N1 - Publisher Copyright:
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2016
Y1 - 2016
N2 - Despite the established role of Ki67 labeling index in prognostic stratification of adrenocortical carcinomas and its recent integration into treatment flow charts, the reproducibility of the assessment method has not been determined. The aim of this study was to investigate interobserver variability among endocrine pathologists using a web-based virtual microscopy approach. Ki67-stained slides of 76 adrenocortical carcinomas were analyzed independently by 14 observers, each according to their method of preference including eyeballing, formal manual counting, and digital image analysis. The interobserver variation was statistically significant (P<0.001) in the absence of any correlation between the various methods. Subsequently, 61 static images were distributed among 15 observers who were instructed to follow a category-based scoring approach. Low levels of interobserver (F=6.99; Fcrit=1.70; P<0.001) as well as intraobserver concordance (n=11; Cohen k ranging from 0.057 to 0.361) were detected. To improve harmonization of Ki67 analysis, we tested the utility of an open-source Galaxy virtual machine application, namely Automated Selection of Hotspots, in 61 virtual slides. The software-provided Ki67 values were validated by digital image analysis in identical images, displaying a strong correlation of 0.96 (P<0.0001) and dividing the cases into 3 classes (cutoffs of 0%-15%-30% and/or 0%-10%-20%) with significantly different overall survivals (P<0.05). We conclude that current practices in Ki67 scoring assessment vary greatly, and interobserver variation sets particular limitations to its clinical utility, especially around clinically relevant cutoff values. Novel digital microscopy-enabled methods could provide critical aid in reducing variation, increasing reproducibility, and improving reliability in the clinical setting.
AB - Despite the established role of Ki67 labeling index in prognostic stratification of adrenocortical carcinomas and its recent integration into treatment flow charts, the reproducibility of the assessment method has not been determined. The aim of this study was to investigate interobserver variability among endocrine pathologists using a web-based virtual microscopy approach. Ki67-stained slides of 76 adrenocortical carcinomas were analyzed independently by 14 observers, each according to their method of preference including eyeballing, formal manual counting, and digital image analysis. The interobserver variation was statistically significant (P<0.001) in the absence of any correlation between the various methods. Subsequently, 61 static images were distributed among 15 observers who were instructed to follow a category-based scoring approach. Low levels of interobserver (F=6.99; Fcrit=1.70; P<0.001) as well as intraobserver concordance (n=11; Cohen k ranging from 0.057 to 0.361) were detected. To improve harmonization of Ki67 analysis, we tested the utility of an open-source Galaxy virtual machine application, namely Automated Selection of Hotspots, in 61 virtual slides. The software-provided Ki67 values were validated by digital image analysis in identical images, displaying a strong correlation of 0.96 (P<0.0001) and dividing the cases into 3 classes (cutoffs of 0%-15%-30% and/or 0%-10%-20%) with significantly different overall survivals (P<0.05). We conclude that current practices in Ki67 scoring assessment vary greatly, and interobserver variation sets particular limitations to its clinical utility, especially around clinically relevant cutoff values. Novel digital microscopy-enabled methods could provide critical aid in reducing variation, increasing reproducibility, and improving reliability in the clinical setting.
KW - Adrenal cortical carcinoma
KW - Digital pathology
KW - Interobserver variation
KW - Ki67 labeling index
KW - Proliferation
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U2 - 10.1097/PAS.0000000000000574
DO - 10.1097/PAS.0000000000000574
M3 - Article
C2 - 26685085
AN - SCOPUS:84962207730
SN - 0147-5185
VL - 40
SP - 569
EP - 576
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 4
ER -