Clinicopathological and Prognostic Implications of Epithelial‐to‐Mesenchymal Transition‐Related Immunohistochemical Markers in Resectable Pancreatic Cancer: A Retrospective Longitudinal Study

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the sixth leading cause of global cancer death. The process of epithelial-to-mesenchymal transition (EMT) is a key driver of early progression and metastasis in PDAC. AIM: Our study aimed to explore the correlation between the expression of EMT markers and survival outcomes. METHODS AND RESULTS: We conducted a retrospective longitudinal study on patients diagnosed with resectable PDAC between January 2005 and June 2019, with a 5-year follow-up for survival analysis. Immunohistochemical staining was performed to assess E-cadherin and vimentin expression. EMT was defined as the presence of high Vimentin (mesenchymal) expression combined with low E-cadherin (epithelial) expression. The study cohort included 135 patients with resectable PDAC, with 86 males (63.7%) and a mean age of 63.5 years (SD 10.1); most tumors were grade 2 (84, 64.6%). Cox regression analysis revealed that Vimentin expression (p = 0.005), positive margin (p = 0.008), and absence of metformin intake (p = 0.023) were independent predictors of poor OS. High Vimentin was associated with lower median OS (17.0 ± 4.4 vs. 25.8 ± 2.3 months, p = 0.037) and DFS (8.6 ± 1.2 vs. 13.0 ± 2.3 months, p = 0.014), compared to low Vimentin, and it was correlated with higher tumor grade (p = 0.028) and metastasis rate (p = 0.032). The poorest outcomes were observed when high Vimentin was coupled with low E-cadherin (median OS of 12.6 ± 4.7 vs. 24.5 ± 2.1 months, p = 0.038; median DFS of 9.5 ± 0.5 vs. 10.8 ± 2.1 months, p = 0.029), compared to the rest of the population. CONCLUSION: Our findings showed that Vimentin overexpression and the EMT phenomenon are strongly associated with poor OS and DFS in resectable PDAC, underscoring their potential as prognostic biomarkers and therapeutic targets.