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

Mod Pathol. 2007 Jan;20(1):120-9. doi: 10.1038/modpathol.3800712. Epub 2006 Nov 24.


HER-2 is the target for antibody based treatment of breast cancer (Herceptin). 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 (HercepTest; DAKO) and fluorescence in situ hybridization (FISH; PathVysion; 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 (P<0.0001, 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((R)) 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.

MeSH terms

  • Adenocarcinoma / chemistry
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / chemistry
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / secondary
  • Esophageal Neoplasms / chemistry
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / pathology*
  • Esophageal Neoplasms / secondary
  • Female
  • Follow-Up Studies
  • Gene Amplification*
  • Gene Expression Regulation, Neoplastic*
  • Genes, erbB-2*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Kaplan-Meier Estimate
  • Male
  • Matched-Pair Analysis
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Receptor, ErbB-2 / analysis*
  • Time Factors
  • Tissue Array Analysis
  • Up-Regulation


  • Receptor, ErbB-2