Tumour budding in solid cancers

Nat Rev Clin Oncol. 2021 Feb;18(2):101-115. doi: 10.1038/s41571-020-0422-y. Epub 2020 Sep 8.


Tumour budding is an emerging prognostic biomarker in colorectal cancer (CRC) and other solid cancers. Tumour buds are usually defined as isolated single cancer cells or clusters of up to four cancer cells located at the invasive tumour front. The prognostic value of tumour budding is now supported by a large body of evidence, whereas the utility of this phenotype as a predictive biomarker remains under investigation. The application of tumour budding indices in clinical practice requires a standardized scoring system that can be tailored to specific tumour types and clinical scenarios. In the context of CRC, tumour budding can be assessed according to the method agreed at the International Tumour Budding Consensus Conference (ITBCC) in 2016. Using the ITBCC scoring system, tumour budding is an independent predictor of lymph node metastasis in patients with pT1 CRC and of unfavourable survival in patients with stage II colon cancer. Regardless of the clinical scenario or tumour type, the assertion that 'the more tumour buds, the worse the clinical outcome' applies. In this Review, we provide an overview of tumour budding in solid cancers, highlighting the molecular and biological aspects of this phenomenon, including its associations with epithelial-mesenchymal transition and features of the tumour microenvironment. We also describe the available evidence demonstrating the value of tumour budding as a biomarker across various solid cancers.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers, Tumor
  • Colorectal Neoplasms / pathology
  • Epithelial-Mesenchymal Transition
  • Female
  • Humans
  • Immunohistochemistry / methods
  • Lymphatic Metastasis / pathology
  • Neoplasm Staging
  • Neoplasms / metabolism
  • Neoplasms / mortality
  • Neoplasms / pathology*
  • Prognosis
  • Tumor Microenvironment


  • Biomarkers, Tumor