title: Annexin A10 optimally differentiates between intrahepatic cholangiocarcinoma and hepatic metastases of pancreatic ductal adenocarcinoma: a comparative study of immunohistochemical markers and panels.
abstract: 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.
authors.affiliation: Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.|Department of Gastroenterology and Hepatology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Kälsch
authors.affiliation: Medizinisches Proteom-Center, Ruhr-Universität Bochum, Universitätsstr 150, 44780, Bochum, Germany.
authors.forename: Juliet
authors.initials: J
authors.lastname: Padden
authors.affiliation: Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Bertram
authors.affiliation: Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.|Medizinisches Proteom-Center, Ruhr-Universität Bochum, Universitätsstr 150, 44780, Bochum, Germany.
authors.forename: Leona L
authors.initials: LL
authors.lastname: Pott
authors.affiliation: Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Reis
authors.affiliation: Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Westerwick
authors.affiliation: Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Christoph M
authors.initials: CM
authors.lastname: Schaefer
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Jan-P
authors.initials: JP
authors.lastname: Sowa
authors.affiliation: Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Dorothe
authors.initials: D
authors.lastname: Möllmann
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Fingas
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dechȇne
authors.affiliation: Medizinisches Proteom-Center, Ruhr-Universität Bochum, Universitätsstr 150, 44780, Bochum, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Sitek
authors.affiliation: Medizinisches Proteom-Center, Ruhr-Universität Bochum, Universitätsstr 150, 44780, Bochum, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Eisenacher
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Ali
authors.initials: A
authors.lastname: Canbay
authors.affiliation: Medizinisches Proteom-Center, Ruhr-Universität Bochum, Universitätsstr 150, 44780, Bochum, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Ahrens
authors.affiliation: Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany. hideo.baba@uk-essen.de.
authors.forename: Hideo A
authors.initials: HA
authors.lastname: Baba
mesh_terms: D017302:Annexins / Q000032:analysis* / Q000096:biosynthesis; D019540:Area Under Curve; D001650:Bile Duct Neoplasms / Q000175:diagnosis*; D014408:Biomarkers, Tumor / Q000032:analysis; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000556:secondary; D018281:Cholangiocarcinoma / Q000175:diagnosis*; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D009362:Neoplasm Metastasis / Q000175:diagnosis*; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000556:secondary; D012372:ROC Curve; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis
chemical_list: C121387:ANXA10 protein, human; D017302:Annexins; D014408:Biomarkers, Tumor
keywords: Annexin A1; Annexin A10; Biomarker; Ductal pancreatic adenocarcinoma; Intrahepatic cholangiocarcinoma