title: Tumor budding in colorectal cancer revisited: results of a multicenter interobserver study.
abstract: 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.
authors.affiliation: Translational Research Unit (TRU), Institute of Pathology, University of Bern, Murtenstr. 31, CH-3010, Bern, Switzerland, viktor.koelzer@pathology.unibe.ch.
authors.forename: Viktor H
authors.initials: VH
authors.lastname: Koelzer
authors.forename: Inti
authors.initials: I
authors.lastname: Zlobec
authors.forename: Martin D
authors.initials: MD
authors.lastname: Berger
authors.forename: Gieri
authors.initials: G
authors.lastname: Cathomas
authors.forename: Heather
authors.initials: H
authors.lastname: Dawson
authors.forename: Klaus
authors.initials: K
authors.lastname: Dirschmid
authors.forename: Marion
authors.initials: M
authors.lastname: Hädrich
authors.forename: Daniel
authors.initials: D
authors.lastname: Inderbitzin
authors.forename: Felix
authors.initials: F
authors.lastname: Offner
authors.forename: Giacomo
authors.initials: G
authors.lastname: Puppa
authors.forename: Walter
authors.initials: W
authors.lastname: Seelentag
authors.forename: Beat
authors.initials: B
authors.lastname: Schnüriger
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lugli
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008875:Middle Aged; D015588:Observer Variation