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Tumor budding in colorectal cancer revisited: results of a multicenter interobserver study

Koelzer, Viktor ; Zlobec, Inti ; Berger, Martin ; Cathomas, Gieri ; Dawson, Heather ; Dirschmid, Klaus ; Hädrich, Marion ; Inderbitzin, Daniel ; Offner, Felix ; Puppa, Giacomo ; Seelentag, Walter ; Schnüriger, Beat ; Tornillo, Luigi ; Lugli, Alessandro

In: Virchows Archiv, 2015, vol. 466, no. 5, p. 485-493

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    Title
    • Tumor budding in colorectal cancer revisited: results of a multicenter interobserver study
    Author
    • Koelzer, Viktor. Translational Research Unit (TRU), Institute of Pathology, University of Bern, Murtenstr. 31, CH-3010, Bern, Switzerland
    • Zlobec, Inti. Translational Research Unit (TRU), Institute of Pathology, University of Bern, Murtenstr. 31, CH-3010, Bern, Switzerland
    • Berger, Martin. Department of Medical Oncology, Bern University Hospital, Bern, Switzerland
    • Cathomas, Gieri. Cantonal Institute of Pathology, Hospital of Baselland, Liestal, Switzerland
    • Dawson, Heather. Translational Research Unit (TRU), Institute of Pathology, University of Bern, Murtenstr. 31, CH-3010, Bern, Switzerland
    • Dirschmid, Klaus. Institute for Pathology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria
    • Hädrich, Marion. Departments of Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland
    • Inderbitzin, Daniel. Departments of Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland
    • Offner, Felix. Institute for Pathology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria
    • Puppa, Giacomo. Service de Pathologie Clinique, Hôpitaux Universitaires de Genève, Genève, Switzerland
    • Seelentag, Walter. Institut de Pathologie Romand (IPR), Lonay, Switzerland
    • Schnüriger, Beat. Departments of Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland
    • Tornillo, Luigi. Institute for Pathology, University Hospital Basel, Basel, Switzerland
    • Lugli, Alessandro. Translational Research Unit (TRU), Institute of Pathology, University of Bern, Murtenstr. 31, CH-3010, Bern, Switzerland
    Document Type
    • Postprint
    OAI-PMH Identifier
    • oai:doc.rero.ch:331644
    Summary
    Tumor budding in colorectal cancer (CRC) is recognized as a valuable prognostic factor but its translation into daily histopathology practice has been delayed by lack of agreement on the optimal method of assessment. Within the context of the Swiss Association of Gastrointestinal Pathology (SAGIP), we performed a multicenter interobserver study on tumor budding, comparing hematoxylin and eosin (H&E) with pan-cytokeratin staining using a 10 high power field (10HPF) and hotspot (1HPF) method. Two serial sections of 50 TNM stage II-IV surgically treated CRC were stained for H&E and pan-cytokeratin. Tumor buds were scored by independent observers at six participating centers in Switzerland and Austria using the 10HPF and 1HPF method on a digital pathology platform. Pearson correlation (r) and intra-class correlation coefficients (ICC) comparing scores between centers were calculated. Three to four times more tumor buds were detected in pan-cytokeratin compared to H&E slides. Correlation coefficients for tumor budding counts between centers ranged from r = 0.46 to r = 0.91 for H&E and from r = 0.73 to r = 0.95 for pan-cytokeratin slides. Interobserver agreement across all centers was excellent for pan-cytokeratin [10HPF: ICC = 0.83 and 1HPF: ICC = 0.8]. In contrast, assessment of tumor budding on H&E slides reached only moderate agreement [10HPF: ICC = 0.58 and 1HPF: ICC = 0.49]. Based on previous literature and our findings, we recommend (1) pan-cytokeratin staining whenever possible, (2) 10HPF method for resection specimens, and (3) 1HPF method for limited material (preoperative biopsy or pT1). Since tumor budding counts can be used to determine probabilities of relevant outcomes and as such more optimally complement clinical decision making, we advocate the avoidance of cutoff scores.