Diagnostic and prognostic significance of RAC3 expression in pancreatic ductal adenocarcinoma: an Immunohistochemical analysis

Ras-related C3 botulinum toxin substrate 3 (RAC3) is frequently up-regulated in multiple malignancies and has been implicated in tumor progression. However, its role in pancreatic ductal adenocarcinoma (PDAC) remains insufficiently defined. This retrospective case–control study included 69 PDAC cases treated with pancreaticoduodenectomy, 46 non-neoplastic pancreatic tissues, and 10 normal pancreatic controls. Immunohistochemical expression of RAC3, TGF-β, and Nestin was evaluated and correlated with clinicopathological parameters and survival outcomes. Results revealed that RAC3 expression was detected in all cases of PDAC. The nuclear RAC3 H-score demonstrated fair diagnostic performance in distinguishing PDAC from non-neoplastic pancreatic tissue (AUC = 0.77). Higher RAC3 H-scores were significantly associated with the absence of perineural invasion (p < 0.001), while increased cytoplasmic RAC3 expression correlated with lower tumor recurrence rates (p = 0.05). Positive expression of TGF-β and Nestin was significantly correlated with the absence of lymphovascular invasion (p = 0.05 and p = 0.002, respectively). Additionally, TGF-β showed a significant association with survival (p = 0.020; HR = 1.0231). In conclussion, RAC3 is frequently expressed in PDAC. Nuclear RAC3 expression may serve as a potential diagnostic marker. However, RAC3 cytoplasmic expression seems to be associated with more favorable clinicopathological features.