Characterization of the immunological microenvironment of tumour buds and its impact on prognosis in mismatch repair-proficient and -deficient colorectal cancers.
OBJECTIVE
Tumour budding in colorectal cancer is established as a poor prognostic factor. The inverse correlation of tumour buds with peritumoural lymphocytic inflammation suggests an interaction with specific immune responses. The aims of this study were to characterize the immunological microenvironment of tumour buds and its impact on prognosis in mismatch repair (MMR)-proficient and -deficient colorectal cancers.


RESULTS
A total of 297 colorectal cancers were double-immunostained for CK22 plus one of the following: CD138, CD16, CD20, CD21, CD56, CD68, CD8, forkhead box P2 (FoxP3), granzyme B, mast cell tryptase, CD3 or T cell intracellular antigen-1 (TIA)-1. Tumour buds and immune cells within the region of densest budding were evaluated [×40 high-power field (HPF)] simultaneously. In both MMR-proficient and -deficient cancers, CD8(+), FoxP3(+) and CD68(+) cells were observed most frequently (>40 cells/HPF) and were independent prognostic factors. A combined prognostic score of tumour budding and CD8(+), FoxP3(+) and CD68(+) distinctly identified patients with low-, moderate- or high-risk colorectal cancers with 5-year survival rates of 75.2% [confidence interval 95% (CI): 66-83], 56.3% (95% CI: 43-68) and 25.2% (95% CI: 14-38), respectively, in MMR-proficient and -deficient cancers.


CONCLUSIONS
The combined assessment of tumour budding with CD8, FoxP3 and CD68 lymphocytes could represent a basis for a prognostic score similar to the Bloom Richardson grade (BRE) and Gleason scores for breast and prostatic cancers.
Institute for Pathology, University Hospital Basel, Basel, Switzerland. inti.zlobec@pathology.unibe.ch
Inti
I
Zlobec
Parham
P
Minoo
Luigi
L
Terracciano
Kristi
K
Baker
Alessandro
A
Lugli
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D053843:DNA Mismatch Repair / Q000235:genetics* / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D016176:T-Lymphocyte Subsets / Q000276:immunology; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein