Detection of Her2/neu gene amplification in hepatocellular carcinoma by fluorescent in situ hybridization

2. SUMMARYHepatocellular carcinoma (HCC) is one of the highly malignant neoplasms witha particulary high incidence in Chinese and African populations. In 2000, HCCranked as the fifth most frequent cancer, but the third leading cause of allcancer deaths worldwide.Several factors are known to play a major role in the development of HCC;Cirrhosis, hepatitis B (HBV), hepatitis C (HCV), and aflatoxin (AFB) areregarded as potential risk factors for hepatocarcinogenesis.Hepatocarcinogenesis involves alterations in the concerted action of proto-oncogenes, growth factors and tumour suppressor genes. Her-2/neu is a proto-oncogene that is localized on chromosome band 17q11.2 .The gene encodestransmembrane tyrosine kinase receptor protein that is a member of theepidermal growth factor receptor (EGFR) with extensive homology to the EGFR.Her-2/neu gene amplification or p185 protein overexpression has been shownin some epithelial tumors and associated with poor prognosis in cancer. It hasbeen shown to correlate with aggressive tumour behavior, and to beoverexpressed in some cancers. The aim of the current study was to investigatethe frequency of Her-2/neu oncogene amplification in primary hepatocellularcarcinoma and reveal its impact on clinicopathological parameters. Thirty sevenparaffin block sections from patients with primary HCC were examined for theirHer-2/neu status. FISH analysis was performed with the Q-biogene Her-2/neuprobe. Her-2/neu amplification was detected in 2(5.40 %) of the 37 primaryHCCs. Also in 3 cases (8.10%), we observed increase in number ofchromosome 17. These patients had grade 2 or 3 tumors with a diameterranging between 3-14 cm and treatment protocols were relevant to tumor sizeand laboratory results.In conclusion, we found overexpression of Her-2/neu in 5.40% of HCCs. Theseresults suggest that Her-2/neu amplification is not the primary mechanism inHCC pathogenesis, however might be one of the factors affecting multistepcarcinogenesis.Key words: Hepatocellular carcinoma, Her-2/neu, fluorescence in situhybridizationiv