Ferrone Cristina R, Ting David T, Shahid Mohammed, Konstantinidis Ioannis T, Sabbatino Francesco, Goyal Lipika, Rice-Stitt Travis, Mubeen Ayesha, Arora Kshitij, Bardeesey Nabeel, Miura John, Gamblin T Clark, Zhu Andrew X, Borger Darrell, Lillemoe Keith D, Rivera Miguel N, Deshpande Vikram
Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Ann Surg Oncol. 2016 Jan;23(1):290-6. doi: 10.1245/s10434-014-4247-8. Epub 2014 Dec 18.
Intrahepatic cholangiocarcinoma (ICC) often is a diagnosis determined by exclusion. Distinguishing ICC from other metastatic adenocarcinomas based on histopathologic or immunohistochemical analysis often is difficult and requires an extensive workup. This study aimed to determine whether albumin, whose expression is restricted to the liver, has potential as a biomarker for ICC using a novel and highly sensitive RNA in situ hybridization (ISH) platform.
Modified branched DNA probes were developed for albumin RNA ISH. The study evaluated 467 patient samples of primary and metastatic lesions.
Of the 467 samples evaluated, 83 were ICCs, 42 were hepatocellular carcinomas (HCCs), and 332 were nonhepatic carcinomas including tumors arising from the perihilar region and bile duct, pancreas, stomach, esophagus, colon, breast, ovary, endometrium, kidney, and urinary bladder. Albumin RNA ISH was highly sensitive for cancers of liver origin, staining positive in 82 (99 %) of 83 ICCs and in 42 HCCs (100 %). Perihilar and distal bile duct carcinomas as well as carcinomas arising at other sites tested negative for albumin. Notably, 6 (22 %) of 27 intrahepatic tumors previously diagnosed as carcinomas of undetermined origin tested positive for albumin.
Albumin RNA ISH is a sensitive and highly specific diagnostic tool for distinguishing ICC from metastatic adenocarcinoma to the liver or carcinoma of unknown origin. Albumin RNA ISH could replace the extensive diagnostic workup, leading to timely confirmation of the ICC diagnosis. Additionally, the assay could serve as a guide to distinguish ICC from perihilar adenocarcinoma.
肝内胆管癌（ICC）的诊断通常是通过排除法确定的。基于组织病理学或免疫组化分析将ICC与其他转移性腺癌区分开来往往很困难，需要进行全面的检查。本研究旨在确定白蛋白（其表达仅限于肝脏）是否具有作为ICC生物标志物的潜力，使用一种新型且高度敏感的RNA原位杂交（ISH）平台。
开发了用于白蛋白RNA ISH的改良分支DNA探针。该研究评估了467例原发性和转移性病变的患者样本。
在评估的467个样本中，83个为ICC，42个为肝细胞癌（HCC），332个为非肝癌，包括肝门周围区域和胆管、胰腺、胃、食管、结肠、乳腺、卵巢、子宫内膜、肾脏和膀胱的肿瘤。白蛋白RNA ISH对肝源性癌症高度敏感，83个ICC中有82个（99%）和42个HCC（100%）呈阳性染色。肝门周围和远端胆管癌以及其他部位发生的癌对白蛋白检测呈阴性。值得注意的是，27个先前诊断为来源不明的肝内肿瘤中有6个（22%）白蛋白检测呈阳性。
白蛋白RNA ISH是一种敏感且高度特异的诊断工具，可用于将ICC与肝转移性腺癌或来源不明的癌区分开来。白蛋白RNA ISH可以取代广泛的诊断检查，从而及时确诊ICC。此外，该检测可作为区分ICC与肝门周围腺癌的指南。
