Frequencies of HER-2/neu expression and gene amplification in patients with oesophageal squamous cell carcinoma.
The utilisation of antitumour T cells induced by cancer vaccination with HER-2 peptides or antibodies (Herceptin) against HER-2, as immunotherapy for oesophageal cancer, is a novel and attractive approach. It is important to clarify the frequencies of HER-2 expression and gene amplification in patients with oesophageal squamous cell carcinoma (SCC) and to evaluate the relationship between HER-2 status and HLA haplotype, since the candidates for HER-2 peptide-based vaccination are restricted to a certain HLA haplotype. We determined the frequency of HER-2 expression using the HercepTest for immunohistochemistry and HER-2 gene amplification by fluorescence in situ hybridisation (FISH) assay in oesophageal SCC (n=66). HER-2-positive tumours (1+/2+/3+) analysed by a HercepTest were observed in 30.3% of all the patients and HER-2 gene amplification evaluated by FISH was observed in 11.0% of all the patients, in which all HercepTest (3+) tumours were found to have gene amplification and three of six moderately positive (2+) tumours showed gene amplification. Furthermore, HER-2-positive cells were present more diffusely and were larger within each tumour in the patients who were HercepTest 3+ than those who were HercepTest 1+. Moreover, the survival rate in HER-2-positive group was significantly worse than that in HER-2-negative group. Also, the survival rate in the patients with HER-2 gene amplification was significantly worse than that without HER-2 gene amplification. In addition, oesophageal SCC patients with both HLA-A24-positive and HER-2-positive tumours (1+/2+/3+) accounted for 26% of these cases, and both HLA-A2- and HER-2-positive tumours accounted for 18% of them.
Mimura
K
K
First Department of Surgery, University of Yamanashi, 1110 Tamaho, Yamanashi 409-3898, Japan.
Kono
K
K
Hanawa
M
M
Mitsui
F
F
Sugai
H
H
Miyagawa
N
N
Ooi
A
A
Fujii
H
H
D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D020869:Gene Expression Profiling; D006680:HLA Antigens; D006239:Haplotypes; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D013601:T-Lymphocytes; D014611:Vaccination
D006680:HLA Antigens; D018719:Erb-b2 Receptor Tyrosine Kinases