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

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., 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 EMT-related markers expression between TB and PDCs indicate that they represent different manifestations of partial EMT. TB seems to be closer to complete EMT than PDCs.