Associations of mucinous differentiation and mucin expression with immune cell infiltration and prognosis in colorectal adenocarcinoma.

Background: The production of extracellular mucus and expression of mucins are commonly aberrant in colorectal cancer, yet their roles in tumour progression remain unclear.

Methods: To investigate the potential influence of mucus on immune response and prognosis, we analysed mucinous differentiation (non-mucinous, 0%; mucinous component, 1-50%; mucinous, >50%) and its associations with immune cell densities (determined with three multiplex immunohistochemistry assays or conventional immunohistochemistry) and survival in 1049 colorectal cancer patients and a validation cohort of 771 patients. We also assessed expression patterns of transmembrane (MUC1, MUC4) and secreted (MUC2, MUC5AC and MUC6) mucins using immunohistochemistry.

Results: Mucinous differentiation was associated with higher densities of CD14HLADR immature monocytic cells and M2-like macrophages in mismatch repair (MMR) proficient tumours, and lower T-cell densities in MMR-deficient tumours. Mucinous differentiation was not associated with cancer-specific survival in multivariable Cox regression models. Higher cytoplasmic MUC1 expression independently predicted worse cancer-specific survival (multivariable HR for high vs. negative to low expression, 2.14; 95% CI: 1.26-3.64). It was also associated with increased myeloid cell infiltration in MMR-proficient tumours.

Conclusions: Although mucinous differentiation did not independently predict survival, extracellular mucus and MUC1 expression could promote tumour progression through immunosuppression.