Diagnostic reproducibility of tumour budding in colorectal cancer: A multicentre, multinational study using virtual microscopy

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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)562-575
Number of pages14
Issue number4
Publication statusPublished - 2012


  • Colorectal cancer
  • Reproducibility
  • Tumour budding
  • Virtual microscopy

ASJC Scopus subject areas

  • Histology
  • Pathology and Forensic Medicine


Dive into the research topics of 'Diagnostic reproducibility of tumour budding in colorectal cancer: A multicentre, multinational study using virtual microscopy'. Together they form a unique fingerprint.

Cite this