Abstract 332: Analysis of HER gene family status in hepatocellular carcinoma by FISH

Abstract

Abstract Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The incidence rate is much higher in developing countries than in industrialized countries. More than 75% of HCC cases occur in the Far East and Southeast Asia. Gene HER1 was known commonly overexpressed in many cancers including HCC. Overexpression of HER1 would lead to cell proliferation, migration, metastasis, antiapoptosis and angiogenesis. Therefore, HER1 has been widely considered as a predict biomarker in clinical purpose. For other epidermal growth factor receptor (EGFR; HER) family members, for example HER2, HER3, and HER4, except the HER1 and HER2, HER3, HER4 are seldom to be studied in HCC so far. To our knowledge, the role of HER3 play a distinct behavior in the EGFR family, which required heterodimerization with other HER family members, then follow to trigger the signaling transduction and, therefore, result in tumor cell proliferation, migration, invasion, anti-apoptosis, and increase angiogenesis. The high level expression of HER3 has been observed in breast, ovarian, and lung cancer etc. Hence, HER3 protein expression in HCC using immunohistochemistry was also showed significantly related to cell proliferation activity, tumor size, intrahepatic metastasis, portal invasion and carcinoma differentiation. Accordingly, we hypothesized that not only HER1 but also HER3 may play an important role in HCC, and the structure of gene and copy number changes may need further investigated. We study the gene expression level of HER1 and HER3 in six HCC cell lines and twenty paraffin tissue samples using fluorescence in situ hybridization (FISH). Their expression level was also correlated with gene structures and/or gene copy number alterations. Our result showed that the gene expression of HER1 consistent the previous reports. Most notably, the gene HER3 presented either the different level of copy number changes or gene structure alterations in all six cell lines. For, most of the clinical samples only gene structure aberrations could be observed. In addition, both gene HER1 and HER3 were highly expressed in Tong cell line when compared to other HCC cell lines. The FISH results showed the alteration of genes structure and increased copy number of gene HER1 and HER3 in all cell lines. While the study on the clinical HCC samples revealed that the gene structural aberrations were more common than gene copy number alterations. However, further evidence from larger clinical samples is needed to clarify our current findings. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 332.