Yeon Seung Chung1, Youngsic Jeon2, Jeong Eun Yoo1,3, Taek Chung4, Hyang Joo Ryu1, Hyunki Kim1, Hyungjin Rhee5, Young Nyun Park6,7. 1. Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. 2. Natural Products Research Center, Korea Institute of Science and Technology (KIST), Gangneung-si, Gangwon-do, Korea. 3. Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea. 4. Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Korea. 5. Department of Radiology, Research Institute of Radiological Science, Center for Clinical Imaging Data Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. hjinrhee@yuhs.ac. 6. Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. young0608@yuhs.ac. 7. Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea. young0608@yuhs.ac.
Abstract
BACKGROUND: The differential diagnosis of intrahepatic cholangiocarcinomas (iCCAs) from metastatic adenocarcinomas from organs adjacent to the liver (gallbladder, pancreas, and stomach) is difficult due to histopathological similarity and a lack of specific markers. This study aimed to develop a method to differentiate iCCA and adenocarcinomas originated from extrahepatic organs adjacent to the liver. METHODS: We retrospectively enrolled surgically resected iCCA (n = 181) and adenocarcinomas from extrahepatic organs (n = 30, n = 28, and n = 38 from gallbladder, pancreas, and stomach, respectively) between 2007 and 2013. The albumin mRNA in situ hybridization (ISH) and immunohistochemistry (IHC) of filamin-A and cytokeratin 19 (CK19) were performed using tissue microarray. Using logistic regression analysis of three markers, iCCA-score was developed, and its diagnostic performance was evaluated. RESULTS: The iCCAs were more frequently positive for albumin ISH (23.2% vs. 0%), filamin-A IHC (47.5% vs. 12.5%) and CK19 (68.5% vs. 40.6%) than extrahepatic adenocarcinomas (p < 0.001 for all). The iCCA-score consisting of these three markers was developed, and it showed higher diagnostic performance (area under the curve [AUC], 0.798 vs. 0.616, p < 0.001). Taking an iCCA-score of 2 or higher as the threshold for iCCA, the sensitivity was substantially higher than albumin ISH alone (45.9% and 23.2%, respectively; p < 0.001), but maintained high specificity (94.8% and 100%, respectively). CONCLUSION: Albumin ISH and IHC staining for filamin-A and CK19 showed distinct expression patterns between iCCA and extrahepatic adenocarcinomas from gallbladder, pancreas, and stomach. We developed iCCA-score that consisted of those three markers, and it showed better diagnostic performance than albumin ISH alone.
BACKGROUND: The differential diagnosis of intrahepatic cholangiocarcinomas (iCCAs) from metastatic adenocarcinomas from organs adjacent to the liver (gallbladder, pancreas, and stomach) is difficult due to histopathological similarity and a lack of specific markers. This study aimed to develop a method to differentiate iCCA and adenocarcinomas originated from extrahepatic organs adjacent to the liver. METHODS: We retrospectively enrolled surgically resected iCCA (n = 181) and adenocarcinomas from extrahepatic organs (n = 30, n = 28, and n = 38 from gallbladder, pancreas, and stomach, respectively) between 2007 and 2013. The albumin mRNA in situ hybridization (ISH) and immunohistochemistry (IHC) of filamin-A and cytokeratin 19 (CK19) were performed using tissue microarray. Using logistic regression analysis of three markers, iCCA-score was developed, and its diagnostic performance was evaluated. RESULTS: The iCCAs were more frequently positive for albumin ISH (23.2% vs. 0%), filamin-A IHC (47.5% vs. 12.5%) and CK19 (68.5% vs. 40.6%) than extrahepatic adenocarcinomas (p < 0.001 for all). The iCCA-score consisting of these three markers was developed, and it showed higher diagnostic performance (area under the curve [AUC], 0.798 vs. 0.616, p < 0.001). Taking an iCCA-score of 2 or higher as the threshold for iCCA, the sensitivity was substantially higher than albumin ISH alone (45.9% and 23.2%, respectively; p < 0.001), but maintained high specificity (94.8% and 100%, respectively). CONCLUSION: Albumin ISH and IHC staining for filamin-A and CK19 showed distinct expression patterns between iCCA and extrahepatic adenocarcinomas from gallbladder, pancreas, and stomach. We developed iCCA-score that consisted of those three markers, and it showed better diagnostic performance than albumin ISH alone.
Authors: John Bridgewater; Peter R Galle; Shahid A Khan; Josep M Llovet; Joong-Won Park; Tushar Patel; Timothy M Pawlik; Gregory J Gores Journal: J Hepatol Date: 2014-03-27 Impact factor: 25.083
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Authors: E Van Cutsem; A Cervantes; R Adam; A Sobrero; J H Van Krieken; D Aderka; E Aranda Aguilar; A Bardelli; A Benson; G Bodoky; F Ciardiello; A D'Hoore; E Diaz-Rubio; J-Y Douillard; M Ducreux; A Falcone; A Grothey; T Gruenberger; K Haustermans; V Heinemann; P Hoff; C-H Köhne; R Labianca; P Laurent-Puig; B Ma; T Maughan; K Muro; N Normanno; P Österlund; W J G Oyen; D Papamichael; G Pentheroudakis; P Pfeiffer; T J Price; C Punt; J Ricke; A Roth; R Salazar; W Scheithauer; H J Schmoll; J Tabernero; J Taïeb; S Tejpar; H Wasan; T Yoshino; A Zaanan; D Arnold Journal: Ann Oncol Date: 2016-07-05 Impact factor: 32.976
Authors: Freddie Bray; Jacques Ferlay; Isabelle Soerjomataram; Rebecca L Siegel; Lindsey A Torre; Ahmedin Jemal Journal: CA Cancer J Clin Date: 2018-09-12 Impact factor: 508.702