Annexin A2 is not a good biomarker for hepatocellular carcinoma in cirrhosis

In China, hepatocellular carcinoma (HCC) usually develops following a long history of chronic hepatitis B infection or cirrhosis. To evaluate the diagnostic role of annexin A2 (ANXA2), a possible tumor marker, in patients with hepatitis B virus (HBV)-related HCC, particularly those with a history of cirrhosis, the present study prospectively enrolled 87 patients with HBV-related HCC (with cirrhosis), 39 patients with HBV-related cirrhosis and 27 healthy controls. The expression levels of serum and tissue ANXA2 were determined using an enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining, respectively. The serum levels of ANXA2 were significantly elevated in the patients with HCC (median, 567.2 μg/ml; P=0.003) and cirrhosis (median, 414.8 μg/ml; P=0.011) compared with the healthy controls (median, 241.9 μg/ml). However, no significant differences were observed in the serum ANXA2 levels between the patients with HCC and those with cirrhosis. The immunohistochemical staining analysis showed that the healthy controls did not show positive staining, while the number of cases immunoreactive for ANXA2 steadily increased from the liver cirrhosis tissues (20/39, 51.3%) to the non-cancer (53/87, 60.9%) and cancer tissues (68/87, 78.2%). The cancer tissues exhibited a significantly higher ANXA2-positive rate compared with the non-cancer (P=0.013) and liver cirrhosis tissues (P=0.002). Furthermore, marked ANXA2 staining was more prevalent in the cancer tissues (16/87, 18.4%) than the non-cancer (4/87, 4.6%; P=0.004) and liver cirrhosis (1/39, 2.6%; P=0.034) tissues. The sensitivity, specificity and diagnostic accuracy of tissue ANXA2 for HCC in cirrhosis were 78.2, 42.1 and 56.8%, respectively. The ANXA2 expression levels in the serum and cancer tissues were not associated with tumor-free survival or patient survival following liver transplantation. Serum or tissue ANXA2 is not a good diagnostic marker for HCC in HBV-related cirrhosis and is not associated with prognosis.