title: Epidermal growth factor receptor gene amplification in surgical resected Japanese lung cancer.
abstract: To evaluate the epidermal growth factor receptor (EGFR) protein expression and increased copy number as predictors of clinical outcome in patients with non-small-cell lung cancer (NSCLC), we have performed fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). We investigated the EGFR increased copy number and EGFR protein expression statuses in 109 surgically treated NSCLC cases. The presence or absence of EGFR mutations of kinase domains was analyzed by genotyping analysis and sequences, and already reported. EGFR increased copy number was defined as Cappuzzo et al. criteria. FISH positive was found from 36/109 (33.0%) lung cancer patients, including 30 high polysomy cases and 6 gene amplification cases. FISH-positive cases were significantly correlated with worse prognosis (log-rank test p=0.0097). Within EGFR-mutant patients (n=55), FISH-positive cases were also correlated with poor prognosis (p=0.0255). FISH-negative tumors were found to be more frequently well-differentiated histology. Smoking status (never smoker vs. smoker, p=0.1510), and gender (p=0.5248) did not correlated with FISH positive. EGFR IHC results were correlated with FISH results (p=0.004), but not correlated with prognosis (p=0.2815). Although EGFR FISH-positive rate did not correlated with EGFR mutation (p=0.1973), EGFR polysomy or amplification cases were correlated with EGFR mutations (p=0.0023). In conclusion, the EGFR FISH-positive rate in Japanese patients with NSCLC was similar to rates in Western populations, unlike the higher frequencies of EGFR mutation in East Asians. A high EGFR gene copy number might have shorter survival in NSCLC.
authors.affiliation: Department of Surgery II, Nagoya City University Medical School, Nagoya 467-8601, Japan. hisasaki@med.nagoya-cu.ac.jp
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shimizu
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Okuda
authors.forename: Osamu
authors.initials: O
authors.lastname: Kawano
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Yukiue
authors.forename: Motoki
authors.initials: M
authors.lastname: Yano
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujii
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics* / Q000601:surgery; D002454:Cell Differentiation; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007564:Japan; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking
chemical_list: D066246:ErbB Receptors