Evidence-Based Medicine
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2014; 20(31): 10908-10915
Published online Aug 21, 2014. doi: 10.3748/wjg.v20.i31.10908
Perinodular ductular reaction/epithelial cell adhesion molecule loss in small hepatic nodules
Qin Zhang, Chuan-Shan Zhang, Qi Xin, Zhe Ma, Gui-Qiu Liu, Bing-Bing Liu, Feng-Mei Wang, Ying-Tang Gao, Zhi Du
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
Feng-Mei Wang, Department of Gastroenterology and Hepatology, the Third Central Hospital of Tianjin Medical University, Tianjin 300170, China
Ying-Tang Gao, Key Laboratory of Artificial Cell, Institute for Hepatobiliary Diseases, the Third Central Hospital of Tianjin Medical University, Tianjin 300170, China
Zhi Du, Department of Hepatobiliary Surgery, Key Laboratory of Artificial Cell, Institute for Hepatobiliary Diseases, the Third Central Hospital of Tianjin Medical University, Tianjin 300170, China
Author contributions: Zhang Q and Zhang CS contributed equally to this work; Zhang Q, Zhang CS and Du Z designed research; Xin Q and Ma Z performed research; Liu GQ and Liu BB analyzed data; Wang FM, Gao YT and Du Z supervised the research process; Zhang Q wrote the paper.
Supported by Key Project of Tianjin Science and Technology Committee, No. 05YFSZSF02500; Foundation of Tianjin, No. 08JCYBJC08300; and Key Research Project of Tianjin Healthy Bureau, No. 11KG112
Correspondence to: Zhi Du, PhD, Professor of Hepatobiliary Surgery, Key Laboratory of Artificial Cell, Institute for Hepatobiliary Diseases, the Third Central Hospital of Tianjin Medical University, No. 83 Jintang Road, Tianjin 300170, China. zhi-du@163.com
Telephone: +86-22-84112366 Fax: +86-22-84112095
Received: February 19, 2014
Revised: May 9, 2014
Accepted: July 11, 2014
Published online: August 21, 2014
Processing time: 181 Days and 22.7 Hours
Abstract

AIM: 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).

CONCLUSION: DR/EpCAM loss may be a useful marker for determining microinvasion in HCCs ≤ 3 cm, but also for predicting prognosis.

Keywords: Ductular reaction; Epithelial cell adhesion molecule; Hepatocellular carcinomas; Small hepatic nodule; Microinvasion; Differential diagnosis

Core tip: Epithelial cell adhesion molecule (EpCAM) may be a new marker of ductular reaction (DR) in routine pathology. We observed the morphological features of DR/EpCAM in 112 small hepatic nodules and compared this with DR/cytokeratin 7 (CK7) and DR/cytokeratin 19 (CK19). The diagnostic value of DR/EpCAM was similar to DR/CK7 and DR/CK19; however, the diagnostic accuracy and specificity increased when these parameters were combined. Therefore, DR/EpCAM loss was confirmed to be a useful marker not only for determining microinvasion in HCCs ≤ 3 cm, but also for predicting prognosis.