Immunohistologic study on the expressions of α-fetoprotein and protein induced by vitamin K absence or antagonist II in surgically resected small hepatocellular carcinoma

Abstract

Sixty-eight cases of single hepatocellular carcinoma (HCC) with less than 3 cm of diameter were immunohistochemically examined for the expressions of ␣-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II). In cancerous tissues, the expression rate was significantly higher for PIVKA-II (34 cases ␣-Fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II) are well known as tumor markers of hepatocellular carcinoma (HCC), and their diagnostic usefulness has been confirmed. Serum levels of tumor markers generally increase along with the increase of tumor size, and most small HCCs at an early stage are not associated with the increases of AFP and PIVKA-II in the serum. In addition, serum AFP could increase slightly in patients with cirrhosis and chronic hepatitis resulting from active liver cell regeneration. Therefore, HCC specificity of serum AFP has been questioned. 1 However, since Breborowicz et al. 2 and Miyazaki et al. 3 demonstrated increases of lens culinaris agglutinin-reactive fraction of AFP in HCC at various levels, AFP that increases in hepatitis and cirrhosis became distinguishable from HCC-related AFP, and the examination of lens culinaris agglutinin-AFP fraction of serum AFP has been reported to be useful for HCC diagnosis. [4][5][6][7] On the other hand, PIVKA-II rarely increases with cirrhosis or chronic hepatitis, and possesses a high specificity to HCC. 8 However, because the serum PIVKA-II-positive rate is low in early-stage small HCC, PIVKA-II had been regarded as less important in clinical diagnosis. This opinion should be changed because of the introduction of a high-sensitivity kit (ED036, Eisai, Tokyo, Japan). 9 In the present study, expressions of AFP and PIVKA-II in the tissues of early-stage small HCC were immunohistochemically examined, and their relationships with tumor size, histologic grade, and serum AFP and PIVKA-II levels were investigated.[ PATIENTS AND MATERIALSAmong the early-stage small HCC nodules, which were surgically resected during 1995 and 1999 at Kurume University Hospital, 68 samples with single HCC nodule with less than 3.0 cm of diameter were subjected for the study. None of the 68 patients had previously received any treatments including transcatheter arterial embolization and percutaneous ethanol injection therapy. The age of the cases ranged from 41 to 86 years, with a mean of 62.7 Ϯ 8.3 (SD) years; there were 50 males and 18 females. All cases, except 1, were examined for virus markers, and 11 cases were hepatitis B surface antigenpositive; 47 cases were hepatitis C virus antibody-positive; 3 cases were positive to both hepatitis B surface antigen and hepatitis C virus antibody, and 6 cases were negative to both. Serum PIVKA-II was measured in 59 cases. Twenty-five of them were examined with a conventional test kit (Eitest MONOP II, Eisai, Co., Ltd.), and 100 mAU/mL was taken as the upper normal limit. The remaining 34 cases were examined with the high-sensitivity kit (ED036, Eisai), and 40 mAU/mL was...

Impact of Preoperative α‐Fetoprotein Level on Disease‐Free Survival After Liver Transplantation for Hepatocellular Carcinoma

“…The higher the AFP level, the earlier did a recurrence appear. Our data confirmed that AFP can be used as a serum marker for tumor aggressiveness [24][25][26][29][30][31][32]. This marker is correlated with the presence of histologic markers of poor prognosis, such as microscopic vascular invasion, presence of satellite nodules, or a poorly differentiated tumor [24][25][26][27].…”

Prognostic Value of Serum AFP, AFP-L3, and GP73 in Monitoring Short-term Treatment Response and Recurrence of Hepatocellular Carcinoma after Radiofrequency Ablation

“…Many studies (Tangkijvanich et al, 2000;Fujioka et al, 2001;Carr et al, 2007;Yamamoto et al, 2010;Saito et al, 2012) revealed that AFP levels > 400 ng/mL were indicative of larger tumor size, greater tumor numbers, a later clinical phase, bile duct invasion, vascular invasion, and a shorter median survival time. Elevated AFP-L3 levels were associated with larger tumor size, a later clinical stage, vascular invasion, poor tumor differentiation, and distant metastasis (Oka et al, 2001;Yoshida et al, 2002;Carr et al, 2007;Saito et al, 2012).…”

Diagnostic performance of alpha-fetoprotein, YKL40 and GP73 in hepatocellular carcinoma Egyptian patients

“…These results are in agreement with Tangkijvanich et al, Fujioka et al, Debruyne and Delanghe, Yamamoto et al and Saito et al who reported an increased level of AFP in HCC patients. [22][23][24][25][26] Elevated AFP levels were associated with larger tumor size, a later clinical stage, vascular invasion, poor tumor differentiation, and distant metastasis. 27 There is a debate in defining the AFP cut off level for the diagnosis of the HCC.…”