title: Correlation between encoded protein overexpression and copy number of the HER2 gene with survival in non-small cell lung cancer.
abstract: The HER2 oncogene, which encodes the tyrosine kinase receptor, is commonly overexpressed in several types of cancer. Treatment using a humanized monoclonal antibody bound to HER2 product is becoming standard therapy for advanced breast cancer. Overexpression occurs in approximately 30% of non-small cell lung cancers (NSCLCs) and has been associated with poor prognosis. However, the frequency of a genetic aberration in the HER2 gene in lung cancer and the association between gene amplification and prognosis are poorly defined. To clarify these relationships, we simultaneously analyzed protein overexpression by immunohistochemistry (IHC) and determined the gene copy number by FISH in 50 surgical specimens of NSCLC. A low-grade increase in the copy number (3 to 8 copies) of the HER2 gene was detected in 44% of tumors. Most represented polysomy of chromosome 17. Protein overexpression was observed in 26%. Overexpression was detected in adenocarcinoma more frequently than in squamous cell carcinoma. No significant correlation was observed between copy number increase and overexpression. Neither gene copy number increase nor overexpression correlated with survival. We conclude that the significance of HER2 status in NSCLC is different from that in breast cancer because high-grade amplification occurs rarely.
authors.affiliation: Department of Surgery, Tokyo Medical University Hospital, Tokyo, Japan. hanakamu@tokyo-med.ac.jp
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Nakamura
authors.forename: Hisashi
authors.initials: H
authors.lastname: Saji
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ogata
authors.forename: Makoto
authors.initials: M
authors.lastname: Hosaka
authors.forename: Masaru
authors.initials: M
authors.lastname: Hagiwara
authors.forename: Norihito
authors.initials: N
authors.lastname: Kawasaki
authors.forename: Harubumi
authors.initials: H
authors.lastname: Kato
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D004273:DNA, Neoplasm / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D004273:DNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases