Abstract
AIMS: Differentiating intrahepatic cholangiocarcinoma (iCCA) from metastatic ductal adenocarcinoma of the pancreas (mPDAC) is challenging due to commonalities in histology and phenotype. Currently, available biomarkers are not completely satisfactory in supporting such differential diagnosis. The present study aims to evaluate aquaporin (AQP)-1 as a reliable biliary biomarker. METHODS AND RESULTS: A total of 151 pancreatobiliary adenocarcinomas, including 77 surgical resections and 74 needle biopsies, were considered, including 84 CCA and 67 PDAC. Immunohistochemistry was performed in two steps: (1) primary tumours, including CCA and PDAC, were compared; (2) data from primary tumours were subsequently validated on needle biopsies, comparing iCCA and mPDAC. The staining was examined according to the immunoreactive score (IRS). On surgical resections, our evaluation showed a mean IRS value of 11.07 in iCCA and 0.7 in PDAC; likewise, on needle biopsies, a mean IRS value of 10.54 in iCCA and 0.97 in mPDAC was observed. Combining surgical resections and needle biopsies, the mean IRS value resulted in 10.76 in iCCA; conversely, it was 0.84 in PDAC. Overall, the ROC curves showed the AQP1 diagnostic performance to be characterized by an AUC of 0.999, being a sensitivity of 100% and a specificity of 95.45%. CONCLUSIONS: AQP1 is a novel biliary biomarker which has been shown to outperform other biliary biomarkers. The main diagnostic scenario in which AQP1 staining should be used is to distinguish iCCA from mPDAC. Furthermore, differential diagnosis between eCCA and PDAC in surgical specimens and between PDAC and CP in needle biopsies should be considered.