Buds, clusters, and transitions in 21st century colorectal carcinoma: revolution or reinvention?

Roger M. Feakins*, Maurice B. Loughrey, Andrew Silver

*Corresponding author for this work

Research output: Contribution to journalComment/debatepeer-review

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Abstract

Invited commentary for Pavlič et al. Tumour budding and poorly differentiated clusters in colon cancer – different manifestations of partial epithelial–mesenchymal transition. J Pathol 2022; 258: 278–288.

Tumour budding (TB) describes single or small groups of neoplastic cells that lack continuity with an advancing tumour front. Poorly differentiated clusters (PDCs) are larger and qualitatively different. TB grade and PDCs may predict a worse outcome in colorectal carcinoma and other cancers and fall into the category of ‘invasive front prognostic markers’ that also includes intratumoural stroma type. Epithelial–mesenchymal transition (EMT) allows the adoption by epithelial cells of mesenchymal characteristics such as dyscohesion, migration, and stromal invasion. TB and PDCs harbor alterations in EMT-related proteins and RNAs and may be morphological manifestations of EMT. However, persistence of epithelioid features and absence of a full complement of typical alterations in TB and PDCs may indicate ‘partial EMT’, i.e. an intermediate/hybrid state. Recently, Pavlič et al asserted that TB and PDCs in colorectal cancer represent different manifestations of partial EMT and, perhaps controversially, that TB is closer than PDCs to complete transition. In clinical practice, low inter-observer agreement for invasive front prognostic markers is a potential problem. The UK colorectal cancer pathology dataset advises assessment of TB and recommends the use of an international consensus system, but time will tell if we are adopting reliable prognostic markers or reinventing the wheel. Additional studies of TB, PDCs, and EMT will presumably allow greater insight into their role in tumour development and progression.
Original languageEnglish
Pages (from-to)121-124
Number of pages4
JournalJournal of Pathology
Volume261
Issue number2
Early online date11 Aug 2023
DOIs
Publication statusPublished - Oct 2023

Keywords

  • epithelial–mesenchymal transition
  • tumour budding
  • poorly differentiated clusters
  • colorectal carcinoma
  • prognosis

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