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


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 gamma2 (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.
Department of Pathology, McGill University, Montreal, Canada.
E
E
Shinto
H
H
Mochizuki
H
H
Ueno
O
O
Matsubara
J R
JR
Jass
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D003593:Cytoplasm / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology*; D009367:Neoplasm Staging / Q000145:classification; D015534:Trans-Activators / Q000032:analysis; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; C400567:LAMC2 protein, human; D007797:Laminin; D015534:Trans-Activators; D051176:beta Catenin