A novel classification of tumour budding in colorectal cancer based on the presence of cytoplasmic pseudo-fragments around budding foci

Aims: Tumour budding is an adverse prognostic factor in colorectal cancer (CRC). We have investigated the significance of cytoplasmic fragments occurring in the immediate vicinity of tumour budding foci. Methods and results: Seventy-three CRCs with high-grade budding (> 10 budding foci in a x 20 objective field) were classified according to extent of budding (10-19 versus 20+ foci) and by the presence or absence of cytoplasmic fragments identified by immunostaining for cytokeratin. In serial sections, cytoplasmic fragments were shown to be dendritic cell processes in continuity with budding tumour cells and were renamed pseudo-fragments. Cytoplasmic pseudo-fragments, but not extent of budding, were associated with aberrant expression of beta-catenin (P = 0.045) and laminin-5 gamma 2 (P < 0.0001), and with absent peritumoral lymphocytic infiltration (P = 0.0077). Cytoplasmic pseudo-fragments had a stronger association with infiltrating growth pattern (P = 0.0014) than extent of tumour budding (P = 0.014). There was no association between extent of budding and cytoplasmic pseudo-fragments (P = 0.12). Conclusions: Cytoplasmic pseudo-fragments may be a marker for an activated budding phenotype that is associated with cell motility and increased invasiveness in CRC and is independent of the extent of budding.