title: Perinodular ductular reaction/epithelial cell adhesion molecule loss in small hepatic nodules.
abstract: OBJECTIVE
  To investigate if loss of epithelial cell adhesion molecule (EpCAM) is associated with microinvasion in hepatocellular carcinomas (HCCs) in the presence of chronic hepatitis B.
  
  
  METHODS
  The expression of EpCAM, cytokeratin 7 (CK7) and CK19 in 112 hepatic nodules was studied, including 20 HCCs with nodules ≤ 3 cm, 26 HCCs with nodules > 3 cm, 20 high-grade dysplastic nodules, 26 cirrhotic, large regenerative nodules and 20 cases of cirrhosis.
  
  
  RESULTS
  Membranes of ductular reaction (DR) hepatobiliary cells, interlobular bile duct and some hepatic cells were positive for EpCAM expression. Active expression of DR/EpCAM was observed in the majority of noninvasive nodules (50/66, 75.76%); however, expression was absent in the major area of invasion in HCCs (42/46, 91.30%). DR/EpCAM loss in HCCs ≤ 3 cm was higher than in high-grade dysplastic nodules (HGDNs) (P < 0.05), cirrhotic, large regenerative nodules and cirrhosis (P < 0.01). Furthermore, patients (20 HCCs ≤ 3 cm, 26 HCCs > 3 cm, 20 HGDNs) with DR/EpCAM expression had a higher overall survival rate (P < 0.01) and lower early recurrence rate (P < 0.01). DR/EpCAM expression showed a close relationship with DR/CK7 and DR/CK19 expression (P < 0.01). The area under the receiver operating characteristic (ROC) curve of DR/EpCAM was similar to that of DR/CK7 and DR/CK19 (P > 0.05). The diagnostic specificity and diagnostic accuracy were both increased when DR/EpCAM, DR/CK7 and DR/CK19 were combined (P < 0.01).
  
  
  CONCLUSIONS
  DR/EpCAM loss may be a useful marker for determining microinvasion in HCCs ≤ 3 cm, but also for predicting prognosis.
authors.affiliation: Qin Zhang, Chuan-Shan Zhang, Qi Xin, Zhe Ma, Gui-Qiu Liu, Bing-Bing Liu, Department of Pathology, the Third Central Hospital of Tianjin Medical University, Tianjin 300170, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Qin Zhang, Chuan-Shan Zhang, Qi Xin, Zhe Ma, Gui-Qiu Liu, Bing-Bing Liu, Department of Pathology, the Third Central Hospital of Tianjin Medical University, Tianjin 300170, China.
authors.forename: Chuan-Shan
authors.initials: CS
authors.lastname: Zhang
authors.affiliation: Qin Zhang, Chuan-Shan Zhang, Qi Xin, Zhe Ma, Gui-Qiu Liu, Bing-Bing Liu, Department of Pathology, the Third Central Hospital of Tianjin Medical University, Tianjin 300170, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xin
authors.affiliation: Qin Zhang, Chuan-Shan Zhang, Qi Xin, Zhe Ma, Gui-Qiu Liu, Bing-Bing Liu, Department of Pathology, the Third Central Hospital of Tianjin Medical University, Tianjin 300170, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Qin Zhang, Chuan-Shan Zhang, Qi Xin, Zhe Ma, Gui-Qiu Liu, Bing-Bing Liu, Department of Pathology, the Third Central Hospital of Tianjin Medical University, Tianjin 300170, China.
authors.forename: Gui-Qiu
authors.initials: GQ
authors.lastname: Liu
authors.affiliation: Qin Zhang, Chuan-Shan Zhang, Qi Xin, Zhe Ma, Gui-Qiu Liu, Bing-Bing Liu, Department of Pathology, the Third Central Hospital of Tianjin Medical University, Tianjin 300170, China.
authors.forename: Bing-Bing
authors.initials: BB
authors.lastname: Liu
authors.affiliation: Qin Zhang, Chuan-Shan Zhang, Qi Xin, Zhe Ma, Gui-Qiu Liu, Bing-Bing Liu, Department of Pathology, the Third Central Hospital of Tianjin Medical University, Tianjin 300170, China.
authors.forename: Feng-Mei
authors.initials: FM
authors.lastname: Wang
authors.affiliation: Qin Zhang, Chuan-Shan Zhang, Qi Xin, Zhe Ma, Gui-Qiu Liu, Bing-Bing Liu, Department of Pathology, the Third Central Hospital of Tianjin Medical University, Tianjin 300170, China.
authors.forename: Ying-Tang
authors.initials: YT
authors.lastname: Gao
authors.affiliation: Qin Zhang, Chuan-Shan Zhang, Qi Xin, Zhe Ma, Gui-Qiu Liu, Bing-Bing Liu, Department of Pathology, the Third Central Hospital of Tianjin Medical University, Tianjin 300170, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Du
mesh_terms: D000951:Antigens, Neoplasm / Q000032:analysis*; D019540:Area Under Curve; D001653:Bile Ducts, Intrahepatic / Q000737:chemistry* / Q000473:pathology* / Q000821:virology; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000821:virology; D015815:Cell Adhesion Molecules / Q000032:analysis*; D018572:Disease-Free Survival; D015536:Down-Regulation; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D053539:Keratin-19 / Q000032:analysis; D053552:Keratin-7 / Q000032:analysis; D008103:Liver Cirrhosis / Q000821:virology; D008113:Liver Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D011237:Predictive Value of Tests; D012372:ROC Curve; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; C507497:KRT7 protein, human; D053539:Keratin-19; D053552:Keratin-7
keywords: Differential diagnosis; Ductular reaction; Epithelial cell adhesion molecule; Hepatocellular carcinomas; Microinvasion; Small hepatic nodule