Des-γ-Carboxyprothrombin (DCP) and NX-DCP Expressions and Their Relationship with Clinicopathological Features in Hepatocellular Carcinoma

Abstract

AimDes-γ-carboxyprothrombin (DCP) has been used as a tumor marker for hepatocellular carcinoma (HCC). Recently the DCP/NX-DCP ratio, calculated by dividing DCP by NX-DCP, has been reported useful in detecting HCC. The purpose of this study is to clarify the significance of DCP and NX-DCP expression in HCC tissues.MethodsHCC and non-HCC tissue samples were obtained from 157 patients and were immunohistochemically examined for DCP and NX-DCP expression using anti-DCP antibody and anti-NX-DCP antibody. DCP and NX-DCP expression scores were calculated by multiplying staining intensity grade by percentage of stained area. Serum DCP and NX-DCP levels were determined in 89 patients. We evaluated the relationship between tumor expression, serum level, and pathomorphological findings.ResultsIntrahepatic metastasis (im) was significantly more frequent in cases with high DCP expression than in cases with low DCP expression. High NX-DCP expression was associated with significantly lower histological grade, and less frequent im or portal vein invasion (vp) than low NX-DCP expression. Serum DCP was correlated with DCP expression, but serum NX-DCP was not correlated with NX-DCP expression. DCP-positive (≥40 mAU/L), NX-DCP-positive (≥90 mAU/L), and DCP/NX-DCP ratio-positive (≥1.5) cases were associated with significantly larger tumor size and more frequent vp than negative cases. DCP was rarely expressed, but NX-DCP was frequently expressed in non-cancerous liver tissues. Patients with NX-DCP expression-negative tumors showed a lower survival rate than those with NX-DCP expression-positive tumors (p = 0.04), whereas the survival in serum NX-DCP-positive cases was lower than that of serum negative cases (p = 0.02).ConclusionsDCP and NX-DCP were produced in HCC tissues, but differed in expression level and biological properties. DCP expression, serum DCP or NX-DCP level, and DCP/NX-DCP ratio were closely related to malignant properties of HCC.

Next-generation des-r-carboxy prothrombin for immunohistochemical assessment of vascular invasion by hepatocellular carcinoma

“…Previous studies have shown that NX-DCP levels were correlated with the degree of fibrosis and HCV infection [ 9 – 12 ]. NX-DCP expression was found in 82% of non-cancerous liver tissues, and overexpression was identified in patients with obstructive jaundice or on warfarin pharmacotherapy [ 16 ]. To avoid such false positives, only patients with a single HCC less than 50 mm in diameter who were not receiving warfarin were examined, and a staining grade based on background parenchyma was used in this immunohistochemical study.…”

“…Recently, in analyses for gene overexpression, some pathways with microvascular invasion have been divided into low and highly invasive phenotypes associated with two distinct gene-expression profiles [ 16 ]. Vascular invasion reflects the biologically aggressive phenotype of HCC, because recurrence is frequent [ 18 – 20 ], and various molecules were up-regulated in the presence of vascular invasion [ 7 , 16 , 24 , 27 ]. Tanaka et al showed two distinct phenotypes in HCC by gene profiling [ 16 ].…”

“…Vascular invasion reflects the biologically aggressive phenotype of HCC, because recurrence is frequent [ 18 – 20 ], and various molecules were up-regulated in the presence of vascular invasion [ 7 , 16 , 24 , 27 ]. Tanaka et al showed two distinct phenotypes in HCC by gene profiling [ 16 ]. They showed that the upregulation of the aurora kinase B-related pathway may be associated with the highly invasive phenotype of HCC by biomolecular network interaction analyses, and overexpression of aurora kinase B protein was confirmed by immunohistochemistry [ 16 , 24 ].…”

“…Patients were divided into two groups, positive and negative for vascular invasion, according to the presence or absence of pathological portal vein invasion. Previous studies have shown that DCP levels were correlated with the degree of fibrosis, hepatitis, and warfarin pharmacotherapy [ 9 – 11 , 16 ]. To avoid false positives, only patients with a single HCC less than 50 mm in diameter who were not on warfarin were examined.…”

“…Conventional DCP has not become a commonly used marker because the value is not accurate in the presence of vitamin K deficiency, the use of anticoagulants, or poor nutritional status associated with alcoholic abuse or jaundice [9][10][11][12]. Therefore, the nextgeneration DCP (NX-DCP) was created to improve on the disadvantage of having to use two different antibodies (P-11 and P-16) [9][10][11][12][13][14][15][16]. The diagnostic accuracy of NX-DCP for HCC under various conditions has been shown in previous studies [9,11,15,17].…”