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


CONCLUSIONS
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.
Riener
Marc-Oliver
MO
Department of Pathology, University Hospital Zurich, Zurich, Switzerland.
Stenner
Frank
F
Liewen
Heike
H
Soll
Christopher
C
Breitenstein
Stefan
S
Pestalozzi
Bernhard Cornelius
BC
Samaras
Panagiotis
P
Probst-Hensch
Nicole
N
Hellerbrand
Claus
C
Müllhaupt
Beat
B
Clavien
Pierre-Alain
PA
Bahra
Marcus
M
Neuhaus
Peter
P
Wild
Peter
P
Fritzsche
Florian
F
Moch
Holger
H
Jochum
Wolfram
W
Kristiansen
Glen
G
D018248:Adenoma, Liver Cell / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000473:pathology; D001652:Bile Ducts / Q000473:pathology; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D020518:Focal Nodular Hyperplasia / Q000378:metabolism*; D006521:Hepatitis, Chronic / Q000097:blood; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D046888:Tissue Array Analysis; D055815:Young Adult
D014408:Biomarkers, Tumor; C410824:GOLM1 protein, human; D008565:Membrane Proteins