Tumour budding in solid cancers

Abstract

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.

Key points

  • Tumour budding is an independent prognostic factor across a variety of solid cancers.

  • In general, the higher the tumour bud count, the worse the clinical outcome.

  • Tumour budding is included as a prognostic factor in published cancer classification guidelines of the Union for International Cancer Control (UICC), the American Joint Committee on Cancer (AJCC) and the World Health Organization (WHO).

  • Grading systems for tumour budding vary between different types of solid cancers.

  • Tumour budding is strongly associated with epithelial–mesenchymal transition and various factors in the tumour microenvironment, where individual tumour buds interact with diverse components of the tumour stroma and immune system.

  • The development of international, evidence-based, standardized scoring systems for tumour budding is essential for future multicentre retrospective clinical studies and prospective randomized clinical trials in order to better define the different prognostic groups.

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Fig. 1: Visualization of tumour budding by immunohistochemistry.
Fig. 2: Key processes involved in the tumour budding phenotype.
Fig. 3: An overview of the prognostic associations of tumour budding in cancers arising at various anatomical sites.

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Acknowledgements

The authors acknowledge research funding from the KWF Kankerbestrijding (Dutch Cancer Society; grant 10602 to A.L., I.Z., R.K. and I.D.N.).

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Lugli, A., Zlobec, I., Berger, M.D. et al. Tumour budding in solid cancers. Nat Rev Clin Oncol (2020). https://doi.org/10.1038/s41571-020-0422-y

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