Comparative Prognostic Roles of β-Catenin Expression and Tumor–Stroma Ratio in Pancreatic Cancer: Neoadjuvant Chemotherapy vs. Upfront Surgery

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 (<i>p</i> = 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%; <i>p</i> = 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, <i>p</i> = 0.043) and UFS (HR = 2.230, <i>p</i> = 0.025) subgroups. High TSR (≥13%) was associated with shorter cancer-specific survival (HR = 2.414, <i>p</i> = 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.