Reproducibility of tumor budding assessment in pancreatic cancer based on a multicenter interobserver study
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ORIGINAL ARTICLE
Reproducibility of tumor budding assessment in pancreatic cancer based on a multicenter interobserver study Eva Karamitopoulou 1 & Irene Esposito 2 & Inti Zlobec 1 & Andrea Cacciato Insilla 2,3 & Martin Wartenberg 1 & David F. Schaeffer 4 & Steve Kalloger 4 & Stefano La Rosa 5 & Christine Sempoux 5 & Irene Ramos Centeno 1 & Philipp Lohneis 6 Received: 16 September 2020 / Revised: 2 November 2020 / Accepted: 3 December 2020 # The Author(s) 2020
Abstract Tumor budding has been reported to be an independent prognostic factor in pancreatic ductal adenocarcinoma (PDAC). Its use in daily diagnostics would improve the prognostic stratification of patients. We performed a multicenter interobserver study to test various budding assessment methods for their reproducibility. Two serial sections of 50 resected, treatment-naïve PDACs were stained for Hematoxylin and Eosin (H&E) and pancytokeratin. Tumor budding was scored by independent observers at five participating centers in Switzerland, Germany, and Canada. Pathologists assessed tumor budding on a digital platform comparing H&E with pancytokeratin staining in 10 high-power fields (10HPF) and one HPF hotspot (1HPF). Additionally, tumor budding was assessed in one H&E hotspot at × 20 magnification, as suggested by the International Tumor Budding Consensus Conference (ITBCC). Correlation coefficients for bud counts between centers ranged from r = 0.58648 to r = 0.78641 for H&E and from r = 0.69288 to r = 0.81764 for pancytokeratin. The highest interobserver agreement across all centers was observed for pancytokeratin 10HPFs (ICC = 0.6). ICC values were 0.49, 0.48, 0.41, and 0.4 for H&E in 1HPF hotspot, H&E in 10HPFs, pancytokeratin in 1HPF, and H&E in one hotspot at ×20, respectively (ITBCC method). This interobserver study reveals a range between moderately poor to moderate agreement levels between pathologists for the different tumor budding assessment methods in PDAC. Acceptable levels of agreement were reached with the pancytokeratin 10HPF method, which can thus be recommended for the assessment of tumor budding in PDAC resection specimens. To improve the levels of interobserver agreement, the implementation of machine learning applications should be considered. Keywords Pancreatic cancer . Tumor budding . Interobserver . Prognosis
Introduction * Eva Karamitopoulou [email protected] 1
Pancreatic Cancer Research Group, Institute of Pathology, University of Bern, Bern, Switzerland
2
Institute of Pathology Heinrich-Heine University & University Hospital, Duesseldorf, Germany
3
Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
4
Department of Pathology & Laboratory Medicine, University of British Columbia and Division of Anatomic Pathology, Vancouver General Hospital, Vancouver, Canada
5
Institute of Pathology, University Hospital and University of Lausanne, Lausanne, Switzerland
6
Faculty of Medicine and University Hospital Cologne, Institute of Pathology, Universi
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