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

• Published in: Modern pathology Vol. 20; no. 1; pp. 120 - 129
• Main Authors: Reichelt, Uta, Duesedau, Peer, Tsourlakis, Maria Ch, Quaas, Alexander, Link, Björn C, Schurr, Paulus G, Kaifi, Jussuf T, Gros, Stephanie J, Yekebas, Emre F, Marx, Andreas, Simon, Ronald, Izbicki, Jakob R, Sauter, Guido
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2007; Elsevier Limited
• Subjects: Adenocarcinoma - chemistry; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adenocarcinoma - secondary; Adult; Aged; Aged, 80 and over; Breast cancer; Carcinoma, Squamous Cell - chemistry; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - secondary; Esophageal cancer; 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; HER-2 amplification and overexpression; Humans; Hybridization; Immunohistochemistry; In Situ Hybridization, Fluorescence; Kaplan-Meier Estimate; Lymphatic system; Male; Matched-Pair Analysis; Medical prognosis; Metastasis; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Pathology; primary and metastatic esophageal carcinomas; Receptor, ErbB-2 - analysis; Thoracic surgery; Time Factors; Tissue Array Analysis; tissue microarray; Tumors; Up-Regulation; United States > US; Germany; primary and metastatic esophageal carcinomas; tissue microarray; HER-2 amplification and overexpression
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/modpathol.3800712

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® 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®.