Serum insulin-like growth factor-II as a serologic marker of small hepatocellular carcinoma

OBJECTIVE: Alpha-fetoprotein (AFP) is not a useful tumor marker for diagnosis of small hepatocellular carcinoma (HCC). There is over-expression of insulin-like growth factor (IGF)-II in HCC tissue. This study investigates the diagnostic application of IGF-II in small HCC. MATERIAL AND METHODS: Serum levels of IGF-II and AFP were determined in 41 patients with small cirrhotic HCC (< or = 3 cm), 41 sex- and age-matched patients with cirrhosis alone (LC), and 41 healthy adults. The optimal cut-off values for diagnosing HCC were determined with receiver operating characteristics (ROC) curve. RESULTS: Both IGF-II and AFP levels in HCC were higher than those in LC patients or controls (each p = 0.0001). The IGF-II levels in LC patients were lower than those in controls (p = 0.001). In HCC patients, multivariate analysis indicated that that both IGF-II (odds ratio, 4.54; 95% confidence interval, 2.15-9.55; p = 0.0001) and AFP (odds ratio, 1.05; 95% confidence interval, 1.01-1.08; p = 0.003) were found to be associated with an increased risk of presence of HCC. The optimal cut-off values of IGF-II (4.1 mg/g prealbumin) and AFP (50 ng/ml) were determined with ROC curves. The sensitivity, specificity, and diagnostic accuracy values for IGF-II were 63%, 90%, and 70%, respectively. Those for AFP were 44%, 95%, and 70%, respectively. Determination of both markers in parallel significantly increase the diagnostic accuracy (88%) and sensitivity (80%), with a high specificity (90%). CONCLUSIONS: Serum IGF-II level can be used as an independent serologic marker or a complementary tumor marker to AFP for diagnosis of small HCC.