Tumour budding and poorly differentiated clusters in colon cancer - different manifestations of partial epithelial-mesenchymal transition

J Pathol. 2022 Nov;258(3):278-288. doi: 10.1002/path.5998. Epub 2022 Sep 5.

Abstract

Morphological features including infiltrative growth, tumour budding (TB), and poorly differentiated clusters (PDCs) have a firmly established negative predictive value in colorectal cancer (CRC). Despite extensive research, the mechanisms underlying different tumour growth patterns remain poorly understood. The aim of this study was to investigate the involvement of epithelial-mesenchymal transition (EMT) in TB and PDCs in CRC. Using laser-capture microdissection, we obtained distinct parts of the primary CRC including TB, PDCs, expansive tumour front, and the central part of the tumour, and analysed the expression of EMT-related markers, i.e. the miR-200 family, ZEB1/2, RND3, and CDH1. In TB, the miR-200 family and CDH1 were significantly downregulated, while ZEB2 was significantly upregulated. In PDCs, miR-141, miR-200c, and CDH1 were significantly downregulated. No significant differences were observed in the expression of any EMT-related markers between the expansive tumour front and the central part of the tumour. Our results suggest that both TB and PDCs are related to partial EMT. Discrete differences in morphology and expression of EMT-related markers between TB and PDCs indicate that they represent different manifestations of partial EMT. TB seems to be closer to complete EMT than PDCs. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Keywords: colon cancer; colorectal cancer; epithelial-mesenchymal transition; miRNA; partial epithelial-mesenchymal transition; poorly differentiated clusters; tumour budding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Colonic Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • United Kingdom

Substances

  • MicroRNAs