Involvement of Membranous S100A10 Expression in the Tumor Budding of Colorectal Cancer: An Immunohistochemical Study

Tumor budding (TB) in colorectal cancer (CRC) has been associated with poor prognosis. TB has been considered a form of epithelial–mesenchymal transition (EMT). Additional discovery of proteins involved in TB can help suppress the aggressiveness of CRC. This study focused on examining whether S100A10, which has been implicated in TB and EMT, qualifies as a biomarker for TB. Formalin-fixed, paraffin-embedded tissue sections from 339 low-grade adenocarcinomas were used. TB was assessed using the recommended hotspot method. Immunohistochemical analysis focused on S100A10 expression on both the tumor buds at the hotspot and tumor glands (TGs), which serve as the direct background for TB, with the stroma-facing membrane (SFM) being the target for the evaluation. Among the 339 patients analyzed, 190 (56.0%) were confirmed to have TB. S100A10 positivity in the tumor buds was detected in 153 patients (80.5%) and was significantly correlated with high-grade TB and high S100A10 positivity in background TGs. S100A10 positivity in background TGs was significantly correlated with high-grade TB, node metastasis, and poor pStage. S100A10 positivity in TGs was often observed in the portions having an irregular border with the stroma, especially ones protruding toward the stroma. In CRC, S100A10 expression at the SFMs of the TGs likely promotes TB from its earliest stage and remains active during TB. The increase in the number of S100A10-expressing tumor cells was associated with poor biological behavior in CRC. Overall, our findings suggest that S100A10 could be a potential biomarker for TB of CRC.