Frequencies of HER-2/neu expression and gene amplification in patients with oesophageal squamous cell carcinoma

Abstract

The utilisation of antitumour T cells induced by cancer vaccination with HER-2 peptides or antibodies (Herceptin) against HER-2, as immunotherapy for oesophageal cancer, is a novel and attractive approach. It is important to clarify the frequencies of HER-2 expression and gene amplification in patients with oesophageal squamous cell carcinoma (SCC) and to evaluate the relationship between HER-2 status and HLA haplotype, since the candidates for HER-2 peptide-based vaccination are restricted to a certain HLA haplotype. We determined the frequency of HER-2 expression using the HercepTestt for immunohistochemistry and HER-2 gene amplification by fluorescence in situ hybridisation (FISH) assay in oesophageal SCC (n ¼ 66). HER-2-positive tumours (1 þ /2 þ /3 þ ) analysed by a HercepTest were observed in 30.3% of all the patients and HER-2 gene amplification evaluated by FISH was observed in 11.0% of all the patients, in which all HercepTest (3 þ ) tumours were found to have gene amplification and three of six moderately positive (2 þ ) tumours showed gene amplification. Furthermore, HER-2-positive cells were present more diffusely and were larger within each tumour in the patients who were HercepTest 3 þ than those who were HercepTest 1 þ . Moreover, the survival rate in HER-2-positive group was significantly worse than that in HER-2-negative group. Also, the survival rate in the patients with HER-2 gene amplification was significantly worse than that without HER-2 gene amplification. In addition, oesophageal SCC patients with both HLA-A24-positive and HER-2-positive tumours (1 þ /2 þ /3 þ ) accounted for 26% of these cases, and both HLA-A2-and HER-2-positive tumours accounted for 18% of them.

Targeting EGFR and HER-2 with cetuximab- and trastuzumab-mediated immunotherapy in oesophageal squamous cell carcinoma

“…With regard to the expression of HER-2 and EGFR on oesophageal SCC, EGFR-positive tumours were observed in 35% of patients with oesophageal SCC, and HER-2-positive tumours were observed in 31% of them in the present study, in line with previous reports (Mimura et al, 2005b). This result was the high-end of the data in literature showing HER-2 expression in oesophageal SCC varying between 0 and 31% (Sunpaweravong et al, 2005), in which the different rate of HER-2 expression seems to be due to the different criteria for evaluating the results.…”

“…In particular, we and others have recently reported that the overexpression of EGFR of oesophageal SCC, partially accounted for by gene amplification, is found in 50 -70% (Itakura et al, 1994;Hanawa et al, 2006), and is indicative of a poor prognosis (Ozawa et al, 1989;Yano et al, 1991). Moreover, we showed that the overexpression of HER-2 in oesophageal SCC was found in 30.3% (Mimura et al, 2005b). These results indicated that oesophageal SCC shows a relatively high incidence of EGFR and/or HER-2 overexpression.…”

Interleukin-21 can efficiently restore impaired antibody-dependent cell-mediated cytotoxicity in patients with oesophageal squamous cell carcinoma

“…In particular, we and others have reported that the overexpression of EGFR is present in 50 -70% of oesophageal squamous cell carcinoma (ESCC) cases, and is indicative of a poor prognosis (Itakura et al, 1994;Hanawa et al, 2006). Moreover, we showed the overexpression of HER2 in 30% of ESCC cases (Mimura et al, 2005a). These results indicate that ESCC cases show a relatively high incidence of EGFR and/or HER2 overexpression, and that the HER family would be an attractive target for the treatment of ESCC.…”

The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis

“…These include increased sensitivity to certain cytotoxic chemotherapeutic agents, resistance to certain hormonal agents and increased propensity to metastasize to the brain (Ross et al, 2003;Gabos et al, 2006). HER2 overexpression and amplification is also seen in subsets of gastric, esophageal and endometrial cancers, also associated with worse disease (Mimura et al, 2005;Morrison et al, 2006;Yano et al, 2006) and also seen rarely in cancers of the oropharynx, lung and bladder (Hirsch et al, 2002;Khan et al, 2002;Latif et al, 2003). The etiologic role of HER2 overexpression in diseases other than breast cancer remain to be defined.…”