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Diagnostic reproducibility of tumour budding in colorectal cancer: a multicentre,multinational study using virtual microscopy
Authors:Giacomo Puppa  Carlo Senore  Kieran Sheahan  Michael Vieth  Alessandro Lugli  Inti Zlobec  Sara Pecori  Lai Mun Wang  Cord Langner  Hiroyuki Mitomi  Takatoshi Nakamura  Masahiko Watanabe  Hideki Ueno  Jacques Chasle  Stephen A Conley  Paulette Herlin  Gregory Y Lauwers  Mauro Risio
Affiliation:1. Division of Pathology, ‘G. Fracastoro’ City Hospital, Verona, Italy;2. AOUS Giovanni Battista, CPO Piemonte, SCDO Epidemiologia dei Tumori, Torino, Italy;3. Department of Histopathology and Centre for Colorectal Disease, St Vincent’s University Hospital School of Medicine and Medical Science, University College Dublin, Dublin, Ireland;4. Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany;5. Institute of Pathology, University of Bern, Bern, Switzerland;6. Department of Pathology, Section of Anatomical Pathology, Policlinico G. B. Rossi, University of Verona, Verona, Italy;7. Department of Cellular Pathology, John Radcliffe Hospital, Headington, Oxford, UK;8. Institute of Pathology, Medical University of Graz, Graz, Austria;9. Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan;10. Department of Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan;11. Department of Surgery, National Defense Medical College, Namiki, Tokorozawa, Saitama, Japan;12. Department of Pathology, Fran?ois Baclesse Comprehensive Cancer Center, Caen, France;13. Pathology Media Lab, Pathology Service, Massachusetts General Hospital, Boston, MA, USA;14. Groupe Régional d’Etudes sur le Cancer, Fran?ois Baclesse Comprehensive Cancer Center, University of Caen, Caen, France;15. Gastrointestinal Pathology Service and Division of Surgical Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA;16. Unit of Pathology, Institute for Cancer Research and Treatment‐IRCC, Candiolo, Torino, Italy
Abstract:Puppa G, Senore C, Sheahan K, Vieth M, Lugli A, Zlobec I, Pecori S, Wang L M, Langner C, Mitomi H, Nakamura T, Watanabe M, Ueno H, Chasle J, Conley S A, Herlin P, Lauwers G Y & Risio M
(2012) Histopathology  61, 562–575 Diagnostic reproducibility of tumour budding in colorectal cancer: a multicentre, multinational study using virtual microscopy Aims: 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. Methods and 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.
Keywords:colorectal cancer  reproducibility  tumour budding  virtual microscopy
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