Clinicopathologic significance of protein induced vitamin K absence or antagonist II and alpha-fetoprotein in hepatocellular carcinoma

Protein induced vitamin K absence or antagonist II (PIVKA-II) and alpha-fet oprotein (AFP) have been considered useful serum markers of hepatocellular carcinoma (HCC). In this study, we examined the clinicopathologic significa nce of these tumour markers in patients with HCCs by measuring their serum levels and performing immunohistochemistry. We studied 349 Japanese patient s with HCCs. Their serum PIVKA-II and AFP levels were determined by enzyme immunoassay before treatment. We examined the correlations between serum PI VKA-II and AFP levels and tumour size, presence of satellite nodules, histo logic HCC grade, and concomitant liver diseases and subjected tumour tissue s to immunohistochemical staining to detect PIVKA-II and AFP expression. Th e serum PIVKA-II levels of patients with poorly differentiated HCCs were si gnificantly higher than those of patients with well and moderately differen tiated HCCs (p<0.05) and they were higher in HCC patients with than without satellite nodules. The serum AFP levels were influenced significantly by c oncomitant liver diseases, but not by the other factors. Immunohistochemica l staining revealed the PIVKA-II expression levels of poorly differentiated HCCs were higher than those of well and moderately differentiated HCCs (p< 0.05). Some HCC cells were PIVKA-II-positive, others were AFP-positive, and some expressed both. The serum PIVKA-II concentration was a better indicat or of HCC than AFP, as it was not influenced by concomitant liver diseases. The presence of PIVKA-II in serum correlated with the presence of satellit e nodules and the histologic HCC grade, a result concordant with the immuno histochemical findings.