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The prognostic value of mucin expression has been reported in several studies. We examined the association between mucin expression and other previously reported prognostic factors, including infiltration of CD10⁺ myeloid cells, transforming growth factor-β1 (TGF-β1) expression, and tumor budding at invasion fronts. Immunohistochemical analysis of 206 colorectal samples was carried out to determine whether MUC1, MUC2, MUC4, and MUC5AC expression could predict the survival of colorectal cancer patients. Serial sections were stained for CD10, TGF-β1, and pan-cytokeratin in order to detect tumor budding. As per multivariate analyses, MUC1 expression appeared to be the most significant predictor of both recurrence-free survival and overall survival. MUC4 was only significant to predict recurrence-free survival, and MUC5AC could be a good marker in stage IV colorectal cancers that require additional chemotherapy. MUC1 (CD227) expression was associated with infiltration of CD10⁺ myeloid cells, TGF-β1 expression, and tumor budding grade. These findings suggest that MUC1 is indicative of poor prognoses that may be associated with immunosuppression and epithelial-mesenchymal transition. Furthermore, MUC1 expression appears to be a chemoattractant for CD10⁺ stromal cells., (© 2013 Japanese Cancer Association.)

The expression of CD10 in tumor cells has been reported to correlate with liver metastasis in colorectal cancer (CRC). However, fibroblasts and immune cells positive for CD10 at the tumor invasion front have not been comprehensively studied. We classified CD10 expression patterns into three types of cells, tumor cells (tCD10), stromal myofibroblasts (sCD10), and immune cells (iCD10), and investigated their correlation with the expression of transforming growth factor-β (TGF-β1) protein and tumor budding grade. Several cell surface markers were stained to detect the phenotype of iCD10(+) cells, including CD3, CD20, CD11b, CD14, CD15, and CD163. Specimens and follow-up data of 206 CRC patients were examined. In multivariate analysis, iCD10 could be an independent prognostic factor for both recurrence-free survival and overall survival in stage I-III CRC (hazard ratio, 2.522 [1.299-4.896], P = 0.006; 2.890 [1.357-6.157], P = 0.006, respectively). The expression of sCD10 and iCD10 was strongly correlated with TGF-β1 expression in tumor cells and tumor budding grade. The phenotype of iCD10(+) cells was CD11b(+) and CD15(+) granulocytes. The infiltration of sCD10(+) fibroblasts and iCD10(+) granulocytes at the tumor invasion front might interact with TGF-β1 protein expression and enhance tumor budding grade. The expression level of iCD10 at the tumor invasion front represented an independent prognostic biomarker in stage I-III CRC and could be integrated into a new staging system., (© 2011 Japanese Cancer Association.)