Usefulness of ED036 kit for measuring serum PIVKA-II levels in small hepatocellular carcinoma

Kuromatsu, Ryoko; Tanaka, Masatoshi; Shimauchi, Yoshihiro; Shimada, Masahiro; Tanikawa, Kyuichi; Watanabe, Keisuke; Yokoo, Takeshi

doi:10.1007/bf02934091

Cited by 43 publications

(39 citation statements)

References 17 publications

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“…However, Saitoh et al (1994) studied the correlation between AFP and PIVKAII measured by the ABC method in patients with small-sized HCC and found no apparent correlation. Kuromatsu and Okuda also detected no obvious correlation between AFP and PIVKAII measured by the revised EIA kit in their HCC patients (Kuromatsu et al, 1997;Okuda et al, 1999). The sensitivity of GGTII in patients without increased AFP was about 62%, which was less than that in Xu et al's (1985) report (84.6%).…”

Section: Discussionmentioning

confidence: 87%

“…In the study of Mita et al (1998), the sensitivities of HCC, small-size HCC, and well-differentiated HCC were also much higher than the sensitivities in the study of Saitoh et al (1994) and our study. Okuda et al (1999), Kuromatsu et al (1997), and Saitoh et al (1994) did not report the sensitivity of PIVKAII in the HCC patients without increased AFP, so we are unable to compare the senstivities. However, Saitoh et al (1994) studied the correlation between AFP and PIVKAII measured by the ABC method in patients with small-sized HCC and found no apparent correlation.…”

Section: Discussionmentioning

confidence: 94%

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Diagnostic value of protein induced by vitamin K absence (PIVKAII) and hepatoma-specific band of serum gamma-glutamyl transferase (GGTII) as hepatocellular carcinoma markers complementary to α-fetoprotein

Zhang

et al. 2003

Br J Cancer

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Serum protein induced by vitamin K absence or antagonist II (PIVKAII), hepatoma-specific band of serum gamma-glutamyl transferase (GGTII), and a-fetoprotein (AFP) levels were determined in 120 patients with hepatocellular carcinoma (HCC) and 90 patients with cirrhosis. The mean serum concentration of PIVKAII in HCC patients was higher than that in cirrhotic patients. A total of 53.3% of patients (64 out of 120) with HCC had PIVKAII levels above 40 mAU ml À1 . However, only 13 patients with cirrhosis had higher PIVKA II levels. Of 32 small HCC patients, 13 (40.6%) had PIVKAII values above 40 mAU ml À1 . An increased concentration of AFP (i.e. 20 ng ml À1 ) was observed in 70 out of 120 (58.3%) patients with HCC and in 33 out of 90 (36.7%) patients with cirrhosis. Positive GGTII was found in 74.0% (89 out of 120) cases of HCC (sensitivity), in 16 of 90 cases of cirrhosis, and 14 of 32 (43.8%) small HCC patients had GGTII positive. No significant correlation was found between serum levels of AFP and PIVKAII. Combining the information from PIVKAII, AFP, and GGTII significantly increases the sensitivity over AFP alone. PIVKAII and GGTII are useful tumour markers complementary to AFP for diagnosis of HCC.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 94%

Diagnostic value of protein induced by vitamin K absence (PIVKAII) and hepatoma-specific band of serum gamma-glutamyl transferase (GGTII) as hepatocellular carcinoma markers complementary to α-fetoprotein

Zhang

et al. 2003

Br J Cancer

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“…[18][19][20] However, the recently developed high-sensitive assay kit realized sufficiently high sensitivity for clinical use as an equivalent to AFP. 9,21 Possible factors or mechanisms of PIVKA-II increase in the serum of HCC patients are: 1) qualitative or quantitative abnormality of prothrombin precursors; 2) changed activity of ␥-glutamyl carboxylase, i.e., the key enzyme of ␥-carboxylation; 3) lack of vitamin K; and 4) abnormality in the vitamin K cycle. 12 PIVKA-II expression in HCC tissues was confirmed by Nohno, 22 Tamano, 23 and Nakagawa et al, 24 but its expression in small HCC has not yet been studied in depth.…”

Section: Discussionmentioning

confidence: 99%

“…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.[ …”

mentioning

confidence: 99%

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

Fujioka

Nakashima

et al. 2001

Hepatology

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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...

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“…In small tumors (Ͻ3 cm) sensitivity of AFP levels varied from 26.9% to 39.3% (6,7). In addition, Des-r-carboxyl prothrombin or serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) and Lens culinaris agglutinin-A AFP (AFP-L3) have been reported to represent highly specific tumor markers when compared with AFP for the early detection of HCC (8,9).…”

Section: Introductionmentioning

confidence: 99%

The Human Cervical Cancer Oncogene Protein Is a Biomarker for Human Hepatocellular Carcinoma

Yoon

Lim²,

Ha³

et al. 2004

Cancer Research

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Human cervical cancer oncogene (HCCR) was identified and appeared to function as a negative regulator of p53 gene. The objective of this study was to validate HCCR expression as a candidate marker for human hepatocellular carcinoma. HCCR epitope was identified as Y 355 LGTRR 360 . According to immunofluorescence study, HCCR was predominantly localized in the plasma membrane and cytoplasm of hepatocellular carcinoma. HCCR proteins were overexpressed in the tumorous compared with the nontumorous cirrhosis tissues. However, HCCR was not detected in normal liver tissue. Concentration of HCCR protein in the serum was measured in a total of 570 subjects, and comparisons were made to ␣-fetoprotein. Serological studies revealed 78.2% sensitivity of HCCR (cutoff value, 15 g/ml), which was significantly higher than 64.6% of ␣-fetoprotein (P ‫؍‬ 0.0098) and 95.7% specificity for hepatocellular carcinoma. Forty of 52 (76.9%) patients with carcinoma negative for ␣-fetoprotein showed positive values for HCCR. A positive rate of 69.2% in carcinoma patients with tumor sizes <2 cm was found to be a higher rate than measurement of ␣-fetoprotein. Furthermore, HCCR expression was also detected in liver cirrhosis at an intermediate level between carcinoma and normal groups, which gave 88.1% sensitivity and 79.0% specificity using 8 g/ml as a cutoff value. In summary, the HCCR assay may have an advantage over the ␣-fetoprotein assay in that it is elevated according to disease progression from liver cirrhosis to carcinoma, and it is more frequently positive in patients with early, small hepatocellular carcinoma.

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Usefulness of ED036 kit for measuring serum PIVKA-II levels in small hepatocellular carcinoma

Cited by 43 publications

References 17 publications

Diagnostic value of protein induced by vitamin K absence (PIVKAII) and hepatoma-specific band of serum gamma-glutamyl transferase (GGTII) as hepatocellular carcinoma markers complementary to α-fetoprotein

Diagnostic value of protein induced by vitamin K absence (PIVKAII) and hepatoma-specific band of serum gamma-glutamyl transferase (GGTII) as hepatocellular carcinoma markers complementary to α-fetoprotein

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

The Human Cervical Cancer Oncogene Protein Is a Biomarker for Human Hepatocellular Carcinoma

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