Annexin A10 meets the challenge of differentiating intrahepatic cholangiocarcinoma from metastatic pancreatic ductal adenocarcinoma. A comparative study of immunohistochemical markers

Aims: Discriminating intrahepatic cholangiocarcinoma (ICC) from hepatic metastases of pancreatic ductal adenocarcinoma (mPDAC) can be challenging. While pathologists still depend on clinicians' anamnestic readings about primary tumor, their diagnosis will lead the patient either to possibly curative operation (for ICC) or to palliation (for mPDAC). Beyond the validation of recently published potential biomarkers for PDAC (primary or metastatic) in a large cohort, we assessed the diagnostic performance of the most promising candidates in the challenging task of discriminating metastatic PDAC (mPDAC) and ICC.

Methods: In a training set of 87 ICC and 88 pPDAC, our by proteomic approach previously identified biomarkers Annexin A1 (ANXA1), ANXA10 and ANXA13 were tested in a comprehensive comparison to 11 published biomarkers or -panels (MUCIN 1, Agrin, S100P, MUC5 AC, Laminin, VHL, CK 17, N-Cadherin, ELAC2, PODXL and HSPG2). The biomarkers with best results were applied to an independent clinical condition set each including biopsies of 27 ICC and 36 mPDAC.

Results: Five markers with the highest AUC values (between 0.72 and 0.84) for the discrimination of ICC and pPDAC, namely Annexin A1, Annexin A10, MUC5 AC, CK17 and N-Cadherin, were applied to liver biopsies containing ICC or mPDAC. Diagnostic characteristics were evaluated for individual markers as well as for 3x panels. ANXA 10 showed the highest diagnostic potential (75.0% and 85.2% correctly classified mPDAC (sensitivity) and ICC (specificity) respectively) of all single markers.

Conclusion: Our results suggest that ANXA10 may be useful meeting the challenging task of differentiating ICC from mPDAC based only upon specimen.