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Albumin, filamin-A and cytokeratin 19 help distinguish intrahepatic cholangiocarcinoma from extrahepatic adenocarcinoma

 Yeon Seung Chung  ;  Youngsic Jeon  ;  Jeong Eun Yoo 1  ;  Taek Chung  ;  Hyang Joo Ryu  ;  Hyunki Kim  ;  Hyungjin Rhee  ;  Young Nyun Park 
 HEPATOLOGY INTERNATIONAL, Vol.17(1) : 77-85, 2023-02 
Journal Title
Issue Date
Adenocarcinoma* / diagnosis ; Adenocarcinoma* / genetics ; Albumins ; Bile Duct Neoplasms* / genetics ; Bile Ducts, Intrahepatic / chemistry ; Bile Ducts, Intrahepatic / metabolism ; Bile Ducts, Intrahepatic / pathology ; Biomarkers, Tumor ; Cholangiocarcinoma* / diagnosis ; Cholangiocarcinoma* / genetics ; Filamins / genetics ; Humans ; Keratin-19 / genetics ; Retrospective Studies
Albumin ; CK19 ; Cholangiocarcinoma ; Diagnosis, Differential ; Extrahepatic adenocarcinoma ; Filamin-A ; Immunohistochemistry ; In situ hybridization ; Neoplasm metastasis ; Pathology
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.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyunki(김현기) ORCID logo https://orcid.org/0000-0003-2292-5584
Ryu, Hyang-Joo(류향주)
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Yoo, Jeong Eun(유정은) ORCID logo https://orcid.org/0000-0001-9990-279X
Rhee, Hyungjin(이형진) ORCID logo https://orcid.org/0000-0001-7759-4458
Chung, Yeon Seung(정연승)
Chung, Taek(정택) ORCID logo https://orcid.org/0000-0001-7567-0680
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