Des-γ-carboxyprothrombin expression in cancer and/or non-cancer liver tissues: Association with survival of patients with resectable hepatocellular carcinoma

Abstract

Des-gamma-carboxyprothrombin (DCP), also known as a protein induced by vitamin K absence or antagonist II, is an abnormal prothrombin. The level of serum DCP is used in clinical diagnosis and prognosis of patients with hepatocellular carcinoma (HCC). Our previous immunohistochemical study showed that DCP is expressed not only in cancer tissues but also in the surrounding non-cancer tissues of HCC patients. However, clinical significance of DCP expression in non-cancer tissues of HCC patients remains unclear. In this study, we examined the relationship between histochemical expression of DCP in cancer and/or non-cancer tissues and the clinical outcome of the HCC patients. A retrospective study was performed of 132 patients each with a single primary HCC nodule. Expression of DCP in tissues was evaluated with immunohistochemical staining using anti-DCP antibody (MU-3). Serum DCP levels were determined using enzyme immunoassay with a double antibody sandwich system. Experimental and clinical data were processed by univariate and multivariate statistical analyses. DCP expression, even if it was observed only in non-cancer tissues, was related to poorer prognosis. Univariate and multivariate analyses showed that DCP expression in cancer and/or non-cancer tissues was a significant prognostic factor. Furthermore, the combined evaluation of tissue DCP expression and serum DCP levels showed that prognosis was poorest for patients showing positive tissue DCP expression and high levels of serum DCP. These results suggest that immunohistochemical evaluation of DCP expression not only in cancer but also in non-cancer tissues serves as a valuable factor in the prognosis of HCC patients and that the combined evaluation of tissue DCP expression and serum DCP level will be more valuable than either factor alone in the effective treatment and prognosis.