Golgi phosphoprotein 2 (GOLPH2) expression in liver tumors... : Hepatology (original) (raw)

Hepatobiliary Malignancies

Golgi phosphoprotein 2 (GOLPH2) expression in liver tumors and its value as a serum marker in hepatocellular carcinomas#

Riener, Marc-Oliver1†; Stenner, Frank2†; Liewen, Heike2; Soll, Christopher3; Breitenstein, Stefan3; Pestalozzi, Bernhard Cornelius2; Samaras, Panagiotis2; Probst-Hensch, Nicole1,4; Hellerbrand, Claus5; Müllhaupt, Beat6; Clavien, Pierre-Alain3; Bahra, Marcus7; Neuhaus, Peter7; Wild, Peter1; Fritzsche, Florian1; Moch, Holger1; Jochum, Wolfram8; Kristiansen, Glen1*‡

1 Department of Pathology, University Hospital Zurich, Zurich, Switzerland

2 Department of Oncology, University Hospital Zurich, Zurich, Switzerland

3 Department of Visceral and Transplantation Surgery, University Hospital Zurich, Zurich, Switzerland

4 Institutes of Social and Preventive Medicine/Surgical Pathology, University Hospital Zurich, Zurich, Switzerland

6 Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland

5 Department of Internal Medicine I, University of Regensburg, Regensburg, Germany

7 Visceral and Transplantation Surgery, University Hospital Charité, Berlin, Germany

8 Institute of Pathology, Kantonsspital St. Gallen, St. Gallen, Switzerland

* Institute for Surgical Pathology, Department of Pathology, University Hospital Zurich (USZ), SchmelzbergstraSe 12, 8091 Zurich, Switzerland

Email:[email protected]

Received August 27, 2008; accepted January 7, 2009.

Published online 16 March 2009 in Wiley InterScience (www.interscience.wiley.com).

Grant sponsor: Zurich Cancer League, Switzerland.

# Potential conflict of interest: Nothing to report.

† These authors contributed equally to this work.

‡ fax: +41 44 255 44 16.

Additional Supporting Information may be found in the online version of this article.

Abstract

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). Conclusion: 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. (Hepatology 2009.)