APC promoter methylation and protein expression in hepatocellular carcinoma.
OBJECTIVE
We investigated the impact of promoter methylation on APC protein expression in patients with hepatocellular carcinoma (HCC).


METHODS
50 patients [HCC (n=19), liver metastasis (n=19), cholangiocellular cancer (n=7), and benign liver tumors (n=5)] were studied for methylation using Methylight analysis. APC mutation was investigated by protein truncation test and direct sequencing of genomic DNA. The protein expression was evaluated by immunohistochemistry and Western blot analysis.


RESULTS
The APC promoter was hypermethylated in 81.8% of non-cancerous liver tissue samples. All HCC samples and ten patients with liver metastasis (52.6%) exhibited APC promoter methylation. The degree of methylation was significantly higher in samples from HCC compared to the non-cancerous liver tissue samples (63.1% vs. 24.98%; p=0.001). The level of APC protein expression was significantly reduced in HCC samples compared to that of the corresponding non-tumor liver tissue (p<0.05).


CONCLUSIONS
Promoter methylation of the APC gene seems to be of significance in hepatocarcinogenesis and results in reduced protein expression in HCC. Interestingly, APC promoter methylation is also present in the vast majority of non-cancerous liver tissue whose (patho)physiological function remains unresolved.
Csepregi
Antal
A
Department of Gastroenterology, Hepatology, and Infectious Diseases, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany. antal.csepregi@medizin.uni-magdeburg.de
Röcken
Christoph
C
Hoffmann
Juliane
J
Gu
Ping
P
Saliger
Stephan
S
Müller
Oliver
O
Schneider-Stock
Regine
R
Kutzner
Nadine
N
Roessner
Albert
A
Malfertheiner
Peter
P
Ebert
Matthias P A
MP
D025601:Adenomatous Polyposis Coli Protein / Q000096:biosynthesis* / Q000235:genetics*; D001483:Base Sequence; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics*
D025601:Adenomatous Polyposis Coli Protein