Virchows Archiv

, Volume 473, Issue 2, pp 189–197 | Cite as

Interobserver variability in the H&E-based assessment of tumor budding in pT3/4 colon cancer: does it affect the prognostic relevance?

  • Benedikt Martin
  • Eva Schäfer
  • Elzbieta Jakubowicz
  • Patrick Mayr
  • Regina Ihringer
  • Matthias Anthuber
  • Gerhard Schenkirsch
  • Tina Schaller
  • Bruno Märkl
Original Article


Tumor budding is a mostly accepted adverse prognostic factor in colorectal carcinoma. It is on the cusp of a widespread use after agreement was reached recently on uniform assessment criteria. We investigated whether the interobserver variability has a direct influence on the prognostic relevance in pT3/4 colon cancer in the background of different levels of experience of the investigators. In total, six investigators with different levels of experience evaluated tumor budding on H&E slides in 244 cases with primary diagnosed (2002–2011) colon carcinoma (pT3/4, N+/−, M0). High-grade tumor budding/budding grade 3 (defined as majority assessment among the investigators) was significantly associated with an adverse outcome (overall survival p = 0.03, cancer-specific survival p = 0.08) and the occurrence of distant metastasis (p = 0.009). However, a detailed analysis of the rating results of the individual investigators revealed that only ratings of one investigator (advanced resident) were associated with an adverse outcome (p = 0.01 cancer-specific survival, overall survival p = 0.09, distant metastasis p = 0.002). The results of another investigator (consultant) were significantly associated with distant metastasis (p = 0.007). The kappa values among the investigators have a range between 0.077 and 0.357 (median 0.166). Total agreement of all investigators existed in 109 cases (44.7%). Our results demonstrate that the evaluation of tumor budding on H&E slides in pT3/4 colon cancer goes along with a considerable interobserver variability among investigators of different levels of experience. Furthermore, our results reveal that these findings directly influence the prognostic value.


Colon cancer Tumor budding Interobserver variability Prognostic factor Histology 



The study was supported by the Hermann-Egger Foundation with 3000 Euro. The Hermann-Egger Foundation is a social foundation, which supports mainly regional projects (incl. science) in Augsburg.

Compliance with ethical standards

The Institutional Review Board of the Hospital Augsburg reviewed and approved the study protocol.

Conflict of interest

All authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of PathologyKlinikum AugsburgAugsburgGermany
  2. 2.Department of Visceral SurgeryKlinikum AugsburgAugsburgGermany
  3. 3.Clinical and Population-Based Cancer Registry AugsburgAugsburgGermany

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