Kälsch Julia, Padden Juliet, Bertram Stefanie, Pott Leona L, Reis Henning, Westerwick Daniela, Schaefer Christoph M, Sowa Jan-P, Möllmann Dorothe, Fingas Christian, Dechȇne Alexander, Sitek Barbara, Eisenacher Martin, Canbay Ali, Ahrens Maike, Baba Hideo A
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.
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.
鉴别肝内胆管癌（ICC）与胰腺导管腺癌肝转移（mPDAC）具有挑战性。虽然病理学家可能依赖于有关原发性肿瘤的临床信息，但他们的诊断将引导患者接受潜在的根治性手术（针对ICC）或姑息治疗（针对mPDAC）。除了在大型队列中验证最近发表的胰腺癌（原发性或转移性）潜在生物标志物外，我们还评估了最有前景的候选标志物在鉴别转移性胰腺癌（mPDAC）与ICC这一具有挑战性任务中的诊断性能。在一个包含87例ICC和88例胰腺原发性导管腺癌（pPDAC）的训练集中，对我们之前鉴定的生物标志物膜联蛋白A1（ANXA1）、膜联蛋白A10和膜联蛋白A13进行了测试，并与11种已发表的生物标志物或标志物组合（粘蛋白1、集聚蛋白、S100P、粘蛋白5AC、层粘连蛋白、VHL、细胞角蛋白17、N-钙黏着蛋白、ELAC2、podocalyxin和硫酸乙酰肝素蛋白聚糖2）进行了比较。在27例ICC和36例mPDAC的独立活检系列中，对结果最佳的生物标志物进行了进一步测试。在训练集中，膜联蛋白A1、膜联蛋白A10、粘蛋白5AC、细胞角蛋白17和N-钙黏着蛋白在鉴别ICC与pPDAC时的AUC值最高（介于0.72和0.84之间）。这些标志物在包含ICC或mPDAC的独立肝活检系列中进行了进一步测试。对单个标志物以及三联标志物组合的诊断特征进行了评估。膜联蛋白A10在所有单个标志物中显示出最高的诊断潜力，正确分类了75%的mPDAC和85%的ICC。我们的结果表明，当只有组织标本可用时，膜联蛋白A10可能有助于区分ICC和mPDAC。
