Transmembrane mucin MUC1 overexpression and its association with CD10⁺ myeloid cells, transforming growth factor-ß1 expression, and tumor budding grade in colorectal cancer.

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-ß1 (TGF-ß1) 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-ß1, 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-ß1 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.

Myeloid cells positive for CD10 at invasion front can predict poor outcome in stage II colorectal cancer.

BACKGROUND: Prediction of poor patient outcome as a effect of adjuvant therapy in stage II colorectal cancer (CRC) remains a matter of controversy. Tumor expression of CD10 and CD15 is reportedly related to poor outcome in CRC. In this study, we investigated whether the expression of CD10 and CD15 is a predictor of outcome and the effect of adjuvant therapy in stage II CRC. MATERIALS AND METHODS: Immunohistochemical analyses for CD10 and CD15 and some additional markers (CD11b, CD14, CD163, CD3, and CD20) were performed using paraffin sections of CRC specimens from 57 patients who had undergone curative surgical treatments between 1998 and 2004. Forty of these patients received postoperative adjuvant therapy. We distinguished between expression in tumor cells (tCD10 and tCD15), in stromal cells (sCD10), and infiltrating immune cells (iCD10 and iCD15). RESULTS: Expression of iCD10 was observed in 21.1% (12/57) of the specimens examined. Of all expression patterns, only iCD10 expression at the cancer invasion front was a useful predictor of a disease-free period and overall survival in stage II CRC. Adjuvant therapy improved the outcome of iCD10(+) patients. CD10(+) immune cells were heterogeneous in origin and partially overlapped the cells positive for myeloid lineage markers, including CD11b and CD15. CONCLUSIONS: iCD10 expression at the tumor invasion front is a useful marker for predicting a high risk of recurrence and mortality in stage II CRCs. CD10(+) immune cells appear to be of myeloid origin.

Prognostic role of CD10⁺ myeloid cells in association with tumor budding at the invasion front of colorectal cancer.

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-ß (TGF-ß1) 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-ß1 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-ß1 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.