Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus.
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.
Reichelt
Uta
U
Department of Pathology, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
Duesedau
Peer
P
Tsourlakis
Maria Ch
MCh
Quaas
Alexander
A
Link
Björn C
BC
Schurr
Paulus G
PG
Kaifi
Jussuf T
JT
Gros
Stephanie J
SJ
Yekebas
Emre F
EF
Marx
Andreas
A
Simon
Ronald
R
Izbicki
Jakob R
JR
Sauter
Guido
G
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
D018719:Erb-b2 Receptor Tyrosine Kinases