Abstract 880: Des-g-carboxyprothrombin (DCP) and NX-DCP expressions and their relationship with clinicopathological features in hepatocellular carcinoma

Abstract

Abstract Aim: Des-g-carboxyprothrombin (DCP) is an abnormal prothrombin and has been used as a tumor marker of hepatocellular carcinoma (HCC). DCP has several variants based on the number of glutamic acid (Glu) residues and their positions in the γ-carboxyglutamic (Gla) domain. DCP expression in HCC tissues has been identified using MU-3 antibody which reacts strongly to DCP containing less Gla residues. Serum DCP also increases in patients with vitamin K deficiency, in which DCP containing more Gla residues (NX-DCP) elevates and can be detected using P-11 or P-16 antibody. Recently, NX-DCP-R, calculated by dividing DCP by NX-DCP, is reportedly useful for the diagnosis of HCC in such patients as taking warfarin. In this study is, we evaluated tissue DCP and NX-DCP expression in HCC. Materials and Methods: Tissue samples of HCC and non-HCC were obtained from 157 patients and were immunohistochemically examined for tissue DCP and NX-DCP expression using MU-3 antibody and P-16 antibody, respectively. Immunostain of HCC was evaluated according to staining intensity and stained area (0-1) within the tumor. The staining intensity was graded into 4 levels (0, negative; 1, weakly; 2, moderately; 3, strongly). The expression score was calculated by multiplying staining intensity grade by stained area. Additionally, serum DCP level and NX-DCP level were determined in 89 patients. We evaluated the relationship among the tissue expression, serum level, and pathomorphological findings. Additionally, immunostain of noncancerous tissues was evaluated according to the stained area. Results: DCP and NX-DCP expressions were found in 69/157 (44%) cases and 35/157 (22%) cases, respectively, in HCC tissue. The expression score of DCP [0.54 ± 0.82 (mean ± SD)] was higher than that of NX-DCP [0.15 ± 0.39]. The DCP expression score was significantly higher in the cases of non-simple nodular type, moderately-poorly differentiated type, and in the cases without capsule formation, and in those with intrahepatic metastasis (im) or portal vein invasion (vp). On the other hand, NX-DCP expression score was significantly higher in the cases of well-differentiated type, and in the cases without im. There was the correlation between serum DCP level and DCP expression score, but there was no correlation between serum NX-DCP level and NX-DCP expression score. DCP-positive (≥40 AU/L) or NX-DCP-R-positive (≥ 1.5) cases were significantly larger in tumor size, higher in histological grade and more frequent in vp than negative cases. In noncancerous liver tissues, DCP was rarely expressed, but NX-DCP was much more frequently expressed. Conclusion: An increase in tissue DCP expression, serum DCP level, and NX-DCP-R was closely related with malignant properties of HCC. In contrast, NX-DCP is less frequently expressed and showed different biological properties from DCP in HCC. Citation Format: Akiko Sumi, Jun Akiba, Sachiko Ogasawara, Masamichi Nakayama, Yoriko Nomura, Sakiko Sanada, Osamu Nakashima, Takuji Torimura, Toshi Abe, Hirohisa Yano. Des-g-carboxyprothrombin (DCP) and NX-DCP expressions and their relationship with clinicopathological features in hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 880. doi:10.1158/1538-7445.AM2014-880