Expression of FXR and HRG and their clinicopathological significance in benign and malignant pancreatic lesions.

aimsThe following study examines the FXR and HRG expression in benign and malignant lesions of the pancreas and evaluates the association between FXR and HRG expression with clinicopathological features and prognosis of pancreatic cancer. MATERIALS AND

methodsImmunohistochemistry of FXR and HRG was performed with EnVision™ in 106 pancreatic ductal adenocarcinoma (PDAC) specimens, 35 paracancer samples (2 cm away from the tumor, when possible or available), 55 benign lesions and 13 normal tissue samples.

resultsThe percentage of cases with positive FXR and negative HRG expression was significantly higher in PDAC compared to pericancerous tissues, benign lesions and normal tissues (P<0.05 or P<0.01). In pancreatic tissues with benign lesions, tissues with positive FXR and/or negative HRG protein expression exhibited dysplasia or intraepithelial neoplasia. The percentage of cases with positive FXR and negative HRG expressions was significantly higher in PDAC with lymph node metastasis, invasion, and TNM stage III+IV disease (P<0.05 or P<0.01). The expression of FXR was negatively correlated with HRG (P<0.05). In addition, the univariate Kaplan-Meier analysis showed that positive FXR and negative HRG expression, poor differentiation, large tumor size, high TNM stage, lymph node metastasis, and invasion were closely associated with decreased overall survival in PDAC patients (P<0.05 or P<0.01). Moreover, multivariate Cox regression analysis identified that positive FXR and negative HRG expression were independent factors for poor prognosis in PDAC. The AUC for FXR was (AUC=0.709, 95% CI: 0.632-0.787), and for HRG was (AUC=0.719, 95% CI: 0.643-0.796) in PDAC compared to benign lesions.

conclusionsPositive FXR and negative HRG expression are closely associated with the carcinogenesis, clinical, pathological and biological behaviors, and poor prognosis in PDAC.