Annexin A10 optimally differentiates between intrahepatic cholangiocarcinoma and hepatic metastases of pancreatic ductal adenocarcinoma: a comparative study of immunohistochemical markers and panels

Virchows Arch. 2017 May;470(5):537-543. doi: 10.1007/s00428-017-2114-2. Epub 2017 Mar 29.


Discriminating intrahepatic cholangiocarcinoma (ICC) from hepatic metastases of pancreatic ductal adenocarcinoma (mPDAC) can be challenging. While pathologists might depend on clinical information regarding a primary tumor, their diagnosis will lead the patient either to potentially curative surgery (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 diagnostic performance of the most promising candidates in the challenging task of discriminating metastatic PDAC (mPDAC) from ICC. In a training set of 87 ICC and 88 pPDAC, our previously identified biomarkers Annexin A1 (ANXA1), ANXA10, and ANXA13 were tested and compared with 11 published biomarkers or panels (MUCIN 1, Agrin, S100P, MUC5 AC, Laminin, VHL, CK 17, N-Cadherin, ELAC2, PODXL and HSPG2). Biomarkers with best results were further tested in an independent series of biopsies of 27 ICC and 36 mPDAC. Highest AUC values (between 0.72 and 0.84) for the discrimination between ICC and pPDAC were found in the training set for Annexin A1, Annexin A10, MUC5 AC, CK17, and N-Cadherin. These markers were further tested on an independent series of liver biopsies containing ICC or mPDAC. Diagnostic characteristics were evaluated for individual markers as well as for 3× panels. ANXA 10 showed the highest diagnostic potential of all single markers, correctly classifying 75% of mPDAC and 85% of ICC. Our results suggest that ANXA10 may be useful to differentiate between ICC and mPDAC, when only a tissue specimen is available.

Keywords: Annexin A1; Annexin A10; Biomarker; Ductal pancreatic adenocarcinoma; Intrahepatic cholangiocarcinoma.

Publication types

  • Comparative Study

MeSH terms

  • Annexins / analysis*
  • Annexins / biosynthesis
  • Area Under Curve
  • Bile Duct Neoplasms / diagnosis*
  • Biomarkers, Tumor / analysis
  • Carcinoma, Pancreatic Ductal / diagnosis*
  • Carcinoma, Pancreatic Ductal / secondary
  • Cholangiocarcinoma / diagnosis*
  • Diagnosis, Differential
  • Humans
  • Immunohistochemistry / methods
  • Neoplasm Metastasis / diagnosis*
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / secondary
  • ROC Curve
  • Sensitivity and Specificity
  • Tissue Array Analysis


  • ANXA10 protein, human
  • Annexins
  • Biomarkers, Tumor