title: Diagnostic reproducibility of tumour budding in colorectal cancer: a multicentre, multinational study using virtual microscopy.
abstract: OBJECTIVE
  Despite the established prognostic relevance of tumour budding in colorectal cancer, the reproducibility of the methods reported for its assessment has not yet been determined, limiting its use and reporting in routine pathology practice.
  
  
  RESULTS
  A morphometric system within telepathology was devised to evaluate the reproducibility of the various methods published for the assessment of tumour budding in colorectal cancer. Five methods were selected to evaluate the diagnostic reproducibility among 10 investigators, using haematoxylin and eosin (H&E) and AE1-3 cytokeratin-immunostained, whole-slide digital scans from 50 pT1-pT4 colorectal cancers. The overall interobserver agreement was fair for all methods, and increased to moderate for pT1 cancers. The intraobserver agreement was also fair for all methods and moderate for pT1 cancers. Agreement was dependent on the participants' experience with tumour budding reporting and performance time. Cytokeratin immunohistochemistry detected a higher percentage of tumour budding-positive cases with all methods compared to H&E-stained slides, but did not influence agreement levels.
  
  
  CONCLUSIONS
  An overall fair level of diagnostic agreement for tumour budding in colorectal cancer was demonstrated, which was significantly higher in early cancer and among experienced gastrointestinal pathologists. Cytokeratin immunostaining facilitated detection of budding cancer cells, but did not result in improved interobserver agreement.
authors: Division of Pathology, 'G. Fracastoro' City Hospital, Verona, ItalyAOUS Giovanni Battista, CPO Piemonte, SCDO Epidemiologia dei Tumori, Torino, ItalyDepartment of Histopathology and Centre for Colorectal Disease, St Vincent's University Hospital School of Medicine and Medical Science, University College Dublin, Dublin, IrelandInstitute of Pathology, Klinikum Bayreuth, Bayreuth, GermanyInstitute of Pathology, University of Bern, Bern, SwitzerlandDepartment of Pathology, Section of Anatomical Pathology, Policlinico G. B. Rossi, University of Verona, Verona, ItalyDepartment of Cellular Pathology, John Radcliffe Hospital, Headington, Oxford, UKInstitute of Pathology, Medical University of Graz, Graz, AustriaDepartment of Human Pathology, Juntendo University School of Medicine, Tokyo, JapanDepartment of Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, JapanDepartment of Surgery, National Defense Medical College, Namiki, Tokorozawa, Saitama, JapanDepartment of Pathology, François Baclesse Comprehensive Cancer Center, Caen, FrancePathology Media Lab, Pathology Service, Massachusetts General Hospital, Boston, MA, USAGroupe Régional d'Etudes sur le Cancer, François Baclesse Comprehensive Cancer Center, University of Caen, Caen, FranceGastrointestinal Pathology Service and Division of Surgical Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USAUnit of Pathology, Institute for Cancer Research and Treatment-IRCC, Candiolo, Torino, Italy.
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mesh_terms: D015179:Colorectal Neoplasms / Q000473:pathology*; D006801:Humans; D008853:Microscopy / Q000379:methods; D015588:Observer Variation; D015203:Reproducibility of Results; D019113:Telepathology / Q000379:methods*