Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus

Abstract

HER-2 is the target for antibody based treatment of breast cancer (Herceptin s ). In order to evaluate the potential role of such a treatment in esophageal cancers, HER-2 amplification and overexpression was investigated in primary and metastatic cancers of the esophagus. A tissue microarray was constructed from 255 primary esophageal cancers (110 adenocarcinomas and 145 squamous cell carcinomas), 89 nodal and 33 distant metastases. Slides were analyzed by immunohistochemistry (HercepTestt; DAKO) and fluorescence in situ hybridization (FISH; PathVysiont; Vysis-Abbott) for HER-2 amplification and overexpression. Amplification was seen in 16/110 (15%) adenocarcinomas and in 7/145 (5%) squamous cell carcinomas. There was a strong association between HER-2 amplification and overexpression, especially in adenocarcinomas (Po0.0001, log rank). There was a 100% concordance of the HER-2 results in primary tumor and corresponding metastases in 84 analyzed pairs. Amplification was typically high-level with more than 10-15 HER-2 copies per tumor cell. Amplification was unrelated to survival, grading, pT, pN, pM or UICC stage. We conclude that esophageal adenocarcinomas belong to those cancer types with relevant frequency high-level HER-2 gene amplification clinical trials or individual case studies investigating the response of metastatic HER-2-positive esophageal cancers to Herceptin s should be undertaken. The strong concordance of the HER-2 status in primary and metastatic cancers argues for a possible response of metastases from patients with HER-2-positive primary tumors to Herceptin s .

Assessment of ErbB2 (Her2) in oesophageal adenocarcinomas: summary of a revised immunohistochemical evaluation system, bright field double in situ hybridisation and fluorescence in situ hybridisation

“…12 In a large study by a different group, the rate of ErbB2 overexpression/amplification was 15%, and no prognostic impact with respect to patients' survival could be demonstrated. 13 Others report similar rates of ErbB2 positivity in oesophageal adenocarcinomas, highlighting the impact of ErbB2 amplification and ERBB2 overexpression during the malignant progression of Barrett's metaplasia to invasive cancer. [27][28][29] The relatively high number of ErbB2-positive cases in our study compared with other reports may be due to the definition of ErbB2 positivity, which was based on the guidelines of the ToGA study and the EMEA for trastuzumab (Herceptin r ) treatment for advanced gastric cancer.…”

“…11,13,15 In this study, we tested ErbB2 status in oesophageal adenocarcinomas by in situ hybridisation (amplification) and immunohistochemistry (expression). A rate of ErbB2 positivity, which was defined 3 þ by immunohistochemistry and/or an ErbB2/Chr17 quotient of Z2 as assessed by in situ hybridisation, could be detected in 29% of the cases.…”

“…ErbB2 amplification was further subclassified into low-level amplification (ErbB2/Chr17 ratio 2-3) and high-level amplification (ErbB2/Chr17 ratio 43), consistent with published studies. 13 Statistical Analysis PASW 18.0 statistical software 11.5 (SPSS Inc., Chicago, IL) was used for statistical analysis. The associations between immunohistochemical expression patterns, the results from in situ hybridisation and the pathologic features were entered into 2 Â 2 tables and evaluated with the w 2 -test.…”

“…The rate of ErbB2 overexpression/amplification in these cancers has been reported at approximately 20-25%, depending on the method of evaluation and the definition used. [11][12][13][14][15] In terms of the relatively high rate of chemotherapy resistance in oesophageal adenocarcinomas, 16,17 additional therapeutic options, such as ErbB2-targeting are of high demand for patients with advanced or metastatic disease.…”

Feasibility of tailored, selective and effective anticancer chemotherapy by direct injection of docetaxel-loaded immunoliposomes into Her2/neu positive gastric tumor xenografts

“…In recent studies, Her2/neu overexpression and/or amplification has been observed, not only in breast cancers, but also in colon (1), bladder (2), ovarian (3), endometrial (4), lung (5), uterine cervix (6), head and neck (7), esophageal (8), and gastric carcinomas (9). The Her2/neu protein has also been reported to be overexpressed in 10-30% of patients with gastric cancer (9,10).…”