Analysis of HER2 gene amplification and protein expression in esophageal squamous cell carcinoma

Abstract

The HER2 gene, which is located on chromosomes 17, is a therapeutic target for cancer. Amplification of HER2 has been described in several tumor types. However, few studies of HER2 gene amplification and protein expression in esophageal carcinoma have been conducted. This study was to investigate the relationship between the expression of HER2/neu and the clinical characteristics, including survival rate, of esophageal squamous carcinoma. The clinical data of 145 patients admitted in Renmin Hospital of Wuhan University, from 2000 to 2005, were reviewed. The HER2 protein expression and gene status in 145 esophageal carcinomas were evaluated using immunohistochemistry and fluorescence in situ hybridization. The survival rate was calculated by the Kaplan-Meier method and the log-rank test using SPSS13.0 software. Compared to normal esophageal epithelium (23/95, 24.2%), HER2 protein was overexpressed in most esophageal squamous carcinoma tissues (60/145, 41.4%), of which 45 (31.0%) were 2+ and 15 (10.4%) were 3+, HER2 overexpression associated significantly with HER2 gene amplification. There is a correlation between the overexpression of HER2 and the differentiation of the carcinoma, the HER2 gene amplification and the differentiation of the carcinoma and the tumor stage. According to univariate analysis, there was a significant difference in survival rates when cases with and without HER-2/neu overexpression or amplification were compared. HER-2/neu amplification/overexpression may be used as an independent prognostic factor in patients with esophageal squamous cancer, and patients with HER-2/neu amplification/overexpression might be potential candidates for new adjuvant therapies that involve the use of humanized monoclonal antibodies.

Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications

“…However, another study by the same authors found that HER2 heterogeneity among HER2 amplified EACs was an independent predictor of worse cancer-specific survival [41]. Apart from EAC, HER2 overexpression was also found to be a negative predictor of survival in esophageal squamous cell carcinoma [42]. …”

HER-2/neu Overxpression in Esophageal Squamous Cell Carcinoma (ESCC) and Its Correlation with Patient’s Clinicopathological Features

“…We found a significant negative correlation between overexpression of HER-2/neu and tumor differentiation which means HER-2/neu overexpression was more common in poorly differentiated ESCC (high grade tumors) versus other grades. A recent study also reported a significant correlation between the overexpression of HER2/neu and the differentiation of the esophageal squamous cell carcinoma (30). In contrast, Raziei et al (6) found that well differentiated tumors overexpress the HER-2/neu protein in patients with gastric cancer.…”

Expression levels of HER2 and MRP1 are not prognostic factors of long-term survival in 829 patients with esophageal squamous cell carcinoma

“…clinicopathological features of patients with ESCC were investigated in the present study. In previous studies, the number of copies of the HER2/neu gene was analyzed by fluorescence or chromogenic in situ hybridization, and the protein expression levels of HER2 were evaluated by IHC (6,7,9,10,12,(16)(17)(18)(19). Previous studies examining the association between the expression levels of HER2 (as determined by IHC) and prognosis in patients with ESCC have reported conflicting results (Table IV).…”

“…Previous studies have observed that the oncogene HER2/neu was overexpressed in 2.0-19.1% cases of ESCC (6)(7)(8)(9)(10)(11)(12)(13), and increased protein expression levels of HER2 have been previously observed in EC (14,15) and ESCC (6,7). However, the role of HER2 in ESCC remains controversial (6,7,9,10,12,(16)(17)(18)(19). Multidrug resistance protein 1 (MRP1), as a member of the adenosine triphosphate-binding cassette transporter family, has been implicated in resistance to cancer therapeutics (20).…”