The interplay between TP53 alterations and Wnt/β-catenin signaling in colorectal cancer (CRC) remains unclear regarding mismatch repair (MMR) status, tumor budding (TB), poorly differentiated cluster (PDC), and prognosis. We analyzed 146 resected CRC cases, quantifying p53, Wnt3, and β-CTN indices and assessing MMR by PMS2 and MSH6 immunohistochemistry. p53 overexpression was associated with younger patients, left-sided tumors, nodal metastasis, and advanced stage, whereas wild-type tumors showed more mucinous differentiation. Deficient MMR was enriched among wild-type p53 cases. Principal component analysis identified distinct axes defined by p53, Wnt3, and β-CTN. Despite comparable Wnt3 levels, nuclear β-CTN accumulation was enhanced in tumors with aberrant (overexpression or null) p53 tumors, with increased TB and PDC indices. Low nuclear β-CTN independently predicted recurrence in stage I–III disease and worse overall survival in proficient MMR tumors (HR 3.07 and 2.52; p = 0.03 for both). A composite score integrating p53 binary status (aberrant vs. wild) with Wnt3 and whole β-CTN indices predicted survival beyond stage; each 1-point increase conferred a 2.56- and 1.77-fold higher risk of cancer-specific and overall mortality (p = 0.004 and 0.04). These findings suggest that p53 dysfunction is associated with alterations in Wnt/β-CTN signaling and that integrating signaling markers with staging may improve prognostic assessment in colorectal cancer.

The benefit of neoadjuvant chemotherapy (NAC) over upfront surgery (UFS) for resectable pancreatic ductal adenocarcinoma (PDAC) is increasingly recognized, yet prognostic biomarkers remain undefined. We evaluated tumor–stroma ratio (TSR), β-catenin (β-CTN) expression, and tumor budding (TB) in 84 resected PDACs (35 NAC, 49 UFS) using digital image analysis of multi-cytokeratin (m-CK) and β-CTN immunohistochemistry. TSR was defined as the proportion of malignant epithelial area within the tumor, and the β-CTN/m-CK index as the ratio of β-CTN to m-CK immunoreactivity in tumor tissue relative to intralobular ducts. TB was significantly less frequent in NAC than UFS (p=0.003), suggesting that NAC may indirectly modulate epithelial–mesenchymal transition, with TB regarded as its morphological correlate. In the NAC cohort, low TSR was associated with more favorable histological response (Evans IIa/IIb, median 7%; Evans I, 16%; p=0.009), likely reflecting NAC-induced tumor shrinkage with relative stromal predominance. In multivariable analysis, low β-CTN/m-CK index (< 0.5) predicted shorter relapse-free survival in both NAC (HR=2.516, p=0.043) and UFS (HR=2.230, p=0.025) subgroups. High TSR (≥13%) was associated with shorter cancer-specific survival (HR=2.414, p=0.034) in the overall cohort, indicating prognostic value complementing its association with NAC response. These results identify β-CTN/m-CK index and TSR as prognostic biomarkers in PDAC.

The benefit of neoadjuvant chemotherapy (NAC) over upfront surgery (UFS) for resectable pancreatic ductal adenocarcinoma (PDAC) is increasingly recognized, yet prognostic biomarkers remain undefined. We evaluated tumor–stroma ratio (TSR), β-catenin (β-CTN) expression, and tumor budding (TB) in 84 resected PDACs (35 NAC, 49 UFS) using digital image analysis of multi-cytokeratin (m-CK) and β-CTN immunohistochemistry. TSR was defined as the proportion of malignant epithelial area within the tumor, and the β-CTN/m-CK index as the ratio of β-CTN to m-CK immunoreactivity in tumor tissue relative to intralobular ducts. TB was significantly less frequent in NAC than UFS (p = 0.003), suggesting that NAC may indirectly modulate epithelial–mesenchymal transition, with TB regarded as its morphological correlate. In the NAC cohort, low TSR was associated with more favorable histological response (Evans IIa/IIb, median 7%; Evans I, 16%; p = 0.009), likely reflecting NAC-induced tumor shrinkage with relative stromal predominance. In multivariable analysis, low β-CTN/m-CK index (<0.5) predicted shorter relapse-free survival in both NAC (HR = 2.516, p = 0.043) and UFS (HR = 2.230, p = 0.025) subgroups. High TSR (≥13%) was associated with shorter cancer-specific survival (HR = 2.414, p = 0.034) in the overall cohort, indicating prognostic value complementing its association with NAC response. These results identify the β-CTN/m-CK index and TSR as prognostic biomarkers in PDAC.