Value of AFP and PIVKA-II in diagnosis of primary hepatocellular carcinoma and prediction of vascular invasion and tumor differentiation

Abstract Background: To explore the value of alpha fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in diagnosis of primary hepatocellular carcinoma (HCC) and their relationship with vascular invasion, tumor differentiation and size. Methods: A total of 433 participants were enrolled in this study including 266 cases with HCC, 87 cases with liver cirrhosis and 80 healthy individuals. Then we explored the correlation between AFP, PIVKA-II serum level and several pathological features such as vascular invasion, tumor differentiation and size. The value of these two markers used singly or jointly in diagnosing HCC was evaluated by receiver operating characteristic (ROC) curve. The ROC curve was also plotted to identify AFP, PIVKA-II serum cut-off values that would best distinguish HCC patients with and without vascular invasion. Results: The level of AFP and PIVKA-II in HCC group was significantly higher (Z was 7.428, 11.243 respectively, all P<0.01). When AFP and PIVKA-II were used as the individual tumor marker, the areas under the ROC curve (AUC) of HCC diagnosis were 0.765 (95% CI, 0.713～0.8170) for AFP, 0.901 (95% CI, 0.868～0.935) for PIVKA-II, and 0.917 (95% CI, 0.886～0.948) for AFP and PIVKA-II simultaneously. The serum levels of AFP and PIVKA-II were positively correlated with tumor differentiation and size. High AFP and PIVKA-II expression was significantly associated with the presence of vascular invasion (P was 0.007 and 0.014 respectively). The AFP level >64.4ng/ml or PIVKA-II level >957.61mAU/ml was the best critical value to predict the presence of vascular invasion. Conclusion: The diagnostic value of AFP and PIVKA-II combined detection or single assay of PIVKA-II is higher than that of separate assay of AFP. And the proper concentration has important clinical value for judging tumor size, tumor cell differentiation and vascular invasion. Above results validate that AFP and PIVKA-II play a significant role in the diagnosis of HCC.