Epithelial-Mesenchymal Transition (EMT) Protein Expression in a Cohort of Stage II Colorectal Cancer Patients With Characterized Tumor Budding and Mismatch Repair Protein Status

Abstract

The relationship between tumor budding, epithelial-mesenchymal transition (EMT) protein expression, and survival has not been closely examined in stage II colorectal cancer (CRC). This study aimed to assess proteins implicated in EMT and to correlate their expression with tumor budding, microsatellite status, and survival. A total of 258 stage II CRCs were identified (tumor budding characterized in 122 cases). Immunohistochemistry for LAMC2, E cadherin, cathepsin L, and β catenin using tissue microarrays was performed. EMT and mismatch repair (MMR) protein expression were correlated with tumor budding and survival. LAMC2 positivity (P < .001) and low membranous β catenin (P = .056) were associated with tumor budding. In a univariate survival analysis, tumor budding (P < .001), LAMC2 positivity (P < .03), and stromal cytoplasmic cathepsin L (P = .025) predicted poorer prognosis. Multivariate analysis showed tumor budding to be the only variable independently associated with survival: hazard ratio = 7.9 (95% confidence interval = 3-21); P < .001. Tumor budding was more frequent in microsatellite-stable (MSS) versus microsatellite-instable (MSI) tumors: 48% versus 26%, respectively; P = .087. MSS cases exhibited reduced membranous β catenin (P = .002) and increased cytoplasmic and nuclear β catenin (P < .001) compared with MSI cases. Epithelial mesenchymal protein expression plays a key role in tumor budding and prognosis in early-stage colorectal cancer and requires further evaluation.