Abstract 4: Gene amplification of EGFR, HER2, HER3 and HER4 in esophageal squamous cell carcinoma

Abstract

Abstract Overexpression of epidermal growth factor receptor (EGFR) and its family members HER2, HER3 and HER4 are found in a variety of human malignancies and their roles in cancer development and progression has been widely recognized for long time. Molecular drugs targeting EGFR family, such as small-molecule inhibitors and specific monoclonal antibodies, are now under intensive investigation in clinical setting. In esophageal squamous cell carcinoma (ESCC), EGFR and HER2 are frequently overexpressed and their poor prognostic impacts have been reported to date. However, there is no study evaluating gene amplification of EGFR, HER2, HER3 and HER4 simultaneously in ESCC in a large cohort. We examined gene amplification of EGFR, HER2, HER3 and HER4 using realtime PCR-based copy number assay on 196 surgical specimens of formalin-fixed, paraffin-embedded (FFPE) samples. Gene amplification of EGFR and HER2 (copy number > 4) was observed in 7 % and 11%, respectively. Although the copy numbers were relatively low, we found gene amplification of HER3 and HER4 to be observed in 8% and 7%, respectively. Gene amplification at least one or more genes was observed in 23 % (45/196) of ESCC samples. Overlapping gene amplification was identified in 8 % (15/196) of samples. In relation with clinical characteristics, gene amplification of HER2 and HER4 was significantly involved in shorter relapse-free survivals in stage III ESCC. In conclusion, gene amplification of EGFR family was frequently observed in ESCC and PCR-based copy number assay could be a powerful tool for detecting gene amplification using FFPE samples. Our results strongly encourage the development of EGFR family-targeted therapy for ESCC with gene amplification. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4. doi:1538-7445.AM2012-4