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High-grade intratumoral tumor budding is a predictor for lymphovascular invasion and adverse outcome in stage II colorectal cancer

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Abstract

Purpose

Evaluation of tumor budding in colorectal cancer (CRC) may help to predict the tumors’ metastatic potential and patients with an aggressive tumor, although not yet metastasized at time of surgery might benefit from adjuvant therapy.

Methods

The degree of intratumoral tumor budding (ITB) was classified as low, intermediate, and high grade according to the recommendations of the International Tumor Budding Consensus Conference (ITBCC) 2016 on H&E and pankeratin-stained TMA sections from 1262 CRC, no special type (NST), including 655 stage II CRC and was correlated to clinicopathological data and overall survival.

Results

Results show that higher ITB rates are significantly linked to higher tumor grade and stage, positive nodal status, lymphovascular invasion (P < 0.0001 each), absence of peritumoral lymphocytes, infiltrating type invasive tumor margin, left-sided cancer localization, and mismatch-repair proficient cancers (P < 0.05 each). In a cohort of 655 stage II CRC, ITB was associated with lymphovascular invasion (P = 0.0459) and adverse clinical outcome (P < 0.0001). In a multivariate analysis including tumor stage, tumor grade, lymphovascular invasion, ITB, and tumor localization, only low tumor stage (P = 0.0022) and absence of lymphovascular invasion (P = 0.0043) showed independent prognostic significance.

Conclusion

In conclusion, our findings argue towards a clinical utility of ITB as a prognostic biomarker in stage II colorectal cancer to define patients who might benefit from adjuvant therapy. ITB might be used as additional or surrogate marker in CRC in which peritumoral tumor budding is difficult to assess.

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Authors and Affiliations

  1. Institute of Pathology, Klinikum Fuerth, Jakob-Henle-Str. 1, 90766, Fuerth, Germany

    Andreas H Marx & Claudius Mickler

  2. Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany

    Guido Sauter, Ronald Simon & Till S Clauditz

  3. Institute of Pathology, University Hospital Basel, 4001, Basel, Switzerland

    Luigi M Terracciano

  4. Department of Surgery, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany

    Jakob R Izbicki

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  1. Andreas H Marx
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Contributions

Andreas H. Marx: conceptualization, methodology, formal analysis, writing–original draft. Claudius Mickler: investigation. Guido Sauter: project administration, supervision. Ronald Simon: formal analysis. Luigi M Terracciano: development or design of methodology, creation of models resources, data curation. Jakob R Izbicki: Resources, data curation. Till S Clauditz: validation, visualization, investigation, writing–review and editing.

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Marx, A.H., Mickler, C., Sauter, G. et al. High-grade intratumoral tumor budding is a predictor for lymphovascular invasion and adverse outcome in stage II colorectal cancer. Int J Colorectal Dis 35, 259–268 (2020). https://doi.org/10.1007/s00384-019-03478-w

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