title: 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). 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.
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Reichelt
authors.forename: Peer
authors.initials: P
authors.lastname: Duesedau
authors.forename: Maria Ch
authors.initials: MCh
authors.lastname: Tsourlakis
authors.forename: Alexander
authors.initials: A
authors.lastname: Quaas
authors.forename: Björn C
authors.initials: BC
authors.lastname: Link
authors.forename: Paulus G
authors.initials: PG
authors.lastname: Schurr
authors.forename: Jussuf T
authors.initials: JT
authors.lastname: Kaifi
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Gros
authors.forename: Emre F
authors.initials: EF
authors.lastname: Yekebas
authors.forename: Andreas
authors.initials: A
authors.lastname: Marx
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D013997:Time Factors; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases