Clinical and Experimental Study of Production of Abnormal Prothrombin PIVKA-II in Hepatocellular Carcinoma.

59%的肝细胞癌（HCC）患者血浆PIVKA-II水平升高。没有一个癫痫患者pivka-ii水平升高。因此，PiVKA-II对HCC具有高特异性。PICKA-II和AFP水平之间没有相关性，表明这两种标志物的组合似乎在HCC的诊断中是有用的。HCC中肿瘤大小和PIVKA-II水平之间存在相关性。HCC患者中PIVKA-II的半衰期为60小时，与vit中的半衰期相同。K缺乏患者，提示HCC患者中的PIVKA-II具有相同的vit。K敏感性与维生素K敏感性相同。缺钾患者因此，在治疗后使用PIVKA-II测量来跟踪HCC患者的半衰期和降低率似乎是有用的。在5种肝癌细胞系的培养物中检测到PIVKA-II，在非肝癌细胞系中未检测到。随着维生素K的加入，PIVKA-II显著降低。因此，PIVKA-II由肝癌细胞产生，其产生依赖于维生素K的量。K可用。利用肝癌细胞株huH-2，我们发现所有3种酶参与正常凝血酶原的产生，K-环氧化物还原酶，K-还原酶（维生素D），K-还原酶（维生素D）。K循环）和-谷氨酰-羧化酶，在huH-2中起作用。血浆PIVKA-II阳性的HCC患者的癌组织显示高水平的PIVKA-II，而非癌组织显示低水平的PIVKA-II。癌组织中凝血酶原相关抗原F-II水平高于非癌组织。PIVKA-II阳性HCC患者的癌组织显示出比PIVKA-II阴性HCC患者更显著的F-II染色。几例肝癌患者的癌组织中存在PIVKA-II阳性染色。因此，提示在肝癌细胞中产生PIVKA-II或F-II。提示HCC中F-II形成增加，导致相对维生素缺乏。钾缺乏和PIVKA-II的出现。

Fifty-nine percent of patients with hepatocellular carcinoma (HCC) had elevated plasma PIVKA-II levels. None of the cirrhotic patients had elevated pivka-ii levels. Thus PiVKA-II has a high specificity for HCC. There was no correlation between PICKA-II and AFP levels indicating that the combination of these 2 markers seems to be useful in the diagnosis of HCC. There was a correlation between tumor size and PIVKA-II levels in HCC. The half-life of PIVKA-II in HCC patients was 60 hr and was identical to that in vit. K deficiency patients, suggesting that PIVKA-II in HCC patients has the same vit. K sensitivity as that in vit. K deficiency patients. Thus it seems useful to follow HCC patients with PIVKA-II measurement after therapy for its half-life and reduction rate. PIVKA-II was detected in the cultures of 5 hepatoma cell lines and was not detected in non-hepatoma cell lines. There was a marked decrease of PIVKA-II with added vit.K.Thus PIVKA-II is produced by hepatoma cells and its production is dependent on the amount of vit. K available. Using hepatoma cell line huH-2, we found out that all 3 enzymes involved in the production of normal prothrombin, K-epoxide-reductase, K-reductase (vit. K cycle) and -glutamyl-carboxylase, functions in huH-2. The cancerous tissue of HCC patients positive for plasma PIVKA-II showed high PIVKA-II levels and the non-cancreous tissur showed low levels. Prothrombin related antigen levels F-II was higher in cancerous tissue than in non-cancerous tissue. The cancerous tissue of PIVKA-II positive HCC patients showed a more marked F-II staining than in PIVKA-II negative HCC patients. There was postitve PIVKA-II staining in the cancerous tissue of several HCC patients. Thus production of either PIVKA-II or F-II was suggested in hepatoma cell. Is was suggested that increased formation of F-II occurs in HCC, resulting in relative vit. K deficiency and appearance of PIVKA-II.