Riener Marc-Oliver, Stenner Frank, Liewen Heike, Soll Christopher, Breitenstein Stefan, Pestalozzi Bernhard Cornelius, Samaras Panagiotis, Probst-Hensch Nicole, Hellerbrand Claus, Müllhaupt Beat, Clavien Pierre-Alain, Bahra Marcus, Neuhaus Peter, Wild Peter, Fritzsche Florian, Moch Holger, Jochum Wolfram, Kristiansen Glen
Department of Pathology, University Hospital Zurich, Zurich, Switzerland.
Hepatology. 2009 May;49(5):1602-9. doi: 10.1002/hep.22843.
Hepatocellular carcinomas (HCCs) and bile duct carcinomas (BDCs) have a poor prognosis. Therefore, surveillance strategies including sensitive and specific serum markers for early detection are needed. Recently, Golgi Phosphoprotein 2 (GOLPH2) has been proposed as a serum marker for HCC, but GOLPH2 expression data in liver tissues was not available. Using tissue microarrays and immunohistochemistry, we semiquantitatively analyzed GOLPH2 protein expression in patients with HCC (n = 170), benign liver tumors (n = 22), BDC (n = 114) and normal liver tissue (n = 105). A newly designed sandwich enzyme-linked immunoassay (ELISA) was used to analyze GOLPH2 levels in the sera of patients with HCC (n = 62), hepatitis C virus (HCV) (n = 29), BDC (n = 10), and healthy control persons (n = 12). By immunohistochemistry 121/170 (71%) of HCC showed strong GOLPH2 expression, which was significantly associated with a higher tumor grade (P = 0.01). A total of 97/114 (85%) BDCs showed a strong GOLPH2 expression which proved to be an independent prognostic factor for overall survival (P < 0.05). Serum levels of GOLPH2 measured by ELISA were significantly elevated in patients with HCC with underlying HCV infection (median 18 mg/L, P < 0.05) and patients with BDC (median = 14.5 mg/L, P < 0.01) in comparison to healthy controls (median 4 mg/L).
GOLPH2 protein is highly expressed in tissues of HCC and BDC. GOLPH2 protein levels are detectable and quantifiable in sera by ELISA. In patients with hepatitis C, serial ELISA measurements in the course of the disease appear to be a promising complementary serum marker in the surveillance of HCC. GOLPH2 should be further evaluated as a serum tumor marker in BDC on a larger scale.
肝细胞癌(HCC)和胆管癌(BDC)预后较差。因此,需要包括用于早期检测的敏感且特异的血清标志物的监测策略。最近,高尔基磷蛋白2(GOLPH2)已被提议作为HCC的血清标志物,但肝脏组织中的GOLPH2表达数据尚不可得。我们使用组织微阵列和免疫组织化学,对170例HCC患者、22例良性肝肿瘤患者、114例BDC患者和105例正常肝组织中的GOLPH2蛋白表达进行了半定量分析。采用新设计的夹心酶联免疫吸附测定(ELISA)法分析了62例HCC患者、29例丙型肝炎病毒(HCV)患者、10例BDC患者和12例健康对照者血清中的GOLPH2水平。通过免疫组织化学检测,121/170(71%)的HCC显示GOLPH2强表达,这与更高的肿瘤分级显著相关(P = 0.01)。总共97/114(85%)的BDC显示GOLPH2强表达,这被证明是总生存期的独立预后因素(P < 0.05)。与健康对照者(中位数4 mg/L)相比,ELISA法测定的HCC合并HCV感染患者(中位数18 mg/L,P < 0.05)和BDC患者(中位数 = 14.5 mg/L,P < 0.01)血清中GOLPH2水平显著升高。
GOLPH2蛋白在HCC和BDC组织中高表达。通过ELISA法可在血清中检测和定量GOLPH2蛋白水平。对于丙型肝炎患者,在疾病过程中进行系列ELISA检测似乎是监测HCC的一种有前景的补充血清标志物。GOLPH2应在更大规模上作为BDC的血清肿瘤标志物进行进一步评估。