Perinodular ductular reaction/epithelial cell adhesion molecule loss in small hepatic nodules

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.