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

## TL;DR

This study finds that measuring β-catenin levels and tumor–stroma ratio in pancreatic cancer can predict cancer recurrence and treatment response, helping guide personalized treatment decisions.

## Contribution

The study identifies β-catenin/m-CK index and tumor–stroma ratio as novel prognostic biomarkers in pancreatic cancer.

## Key findings

- Low β-catenin levels predict shorter relapse-free survival in both chemotherapy and surgery subgroups.
- High tumor–stroma ratio is associated with shorter cancer-specific survival in pancreatic cancer patients.
- Neoadjuvant chemotherapy reduces tumor budding, suggesting a modulation of invasive growth.

## Abstract

Pancreatic cancer is one of the most aggressive cancers, and doctors need better ways to estimate which patients may relapse after surgery. In this study, we analyzed tissue samples from 84 patients, some who received chemotherapy before surgery and some who went straight to surgery. Using computer-based imaging, we looked at several microscopic features. First, we measured β-catenin, a protein that helps cells stick together, and found that patients with low levels were more likely to experience cancer recurrence. We also examined the tumor–stroma ratio (TSR), the balance between cancer cells and surrounding supportive tissue, which showed important links with treatment response and survival. Finally, we evaluated tumor budding, small groups of cells that indicate invasive growth, and found that chemotherapy before surgery reduced this feature. These results suggest that simple microscopic tests can help predict outcomes and guide more personalized treatment for people with pancreatic 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 the β-CTN/m-CK index and TSR as prognostic biomarkers in PDAC.