title: Clinicopathological and Survival Analysis of Japanese Patients with Resected Non-Small-Cell Lung Cancer Harboring NKX2-1, SETDB1, MET, HER2, SOX2, FGFR1, or PIK3CA Gene Amplification.
abstract: BACKGROUND
  Gene amplification is an important genetic change in cancer cells. We investigated the prevalence, clinicopathological characteristics, and prognostic value of NKX2-1 (also known as TTF-1), SETDB1, MET, HER2, SOX2, FGFR1, and PIK3CA amplification in Japanese patients with non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  The copy numbers of the seven above-mentioned genes were assessed using fluorescence in situ hybridization in a tissue microarray containing 282 surgically resected NSCLC specimens (164 adenocarcinoma [AC], 99 squamous cell carcinoma [SCC], and 19 others). Clinicopathological information were obtained from the medical records.
  
  
  RESULTS
  NKX2-1, SETDB1, MET, HER2, SOX2, FGFR1, and PIK3CA gene amplification were observed in 30 of 277 (10.8%), 16 of 280 (5.7%), 38 of 278 (13.7%), 8 of 270 (3.0%), 34 of 278 (12.2%), 18 of 282 (6.4%), and 53 of 278 (19.1%) cases, respectively. Coamplification was detected in 16 of 156 (10.3%) AC patients and 35 of 93 (37.6%) SCC patients (p < 0.0001). NKX2-1 amplification was significantly related to an AC histology (p = 0.004), whereas SOX2, FGFR1, and PIK3CA amplifications were related to a SCC histology (p < 0.0001). Within the ACs, NKX2-1 and SETDB1 amplifications were markers of a shorter survival period. A multivariate Cox proportional hazards model revealed that NKX2-1 amplification was an independent predictor of poor survival (hazard ratio, 2.938; 95% confidence interval, 1.434-6.022; p = 0.003). Coamplification had impact on patient outcome in AC but not in entire NSCLC and SCC.
  
  
  CONCLUSIONS
  The amplification status differed among the histological types of NSCLC. NKX2-1 amplification was an independent and the most practically important predictor of a poor prognosis among Japanese patients with AC.
authors.affiliation: *Department of Tumor Pathology, †Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan; ‡Department of Pathology, Hamamatsu Medical Center, Hamamatsu, Shizuoka, Japan; §First Department of Surgery, ‖Clinical Oncology, ¶Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Inoue
authors.forename: Shun
authors.initials: S
authors.lastname: Matsuura
authors.forename: Nobuya
authors.initials: N
authors.lastname: Kurabe
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kahyo
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mori
authors.forename: Akikazu
authors.initials: A
authors.lastname: Kawase
authors.forename: Masato
authors.initials: M
authors.lastname: Karayama
authors.forename: Naoki
authors.initials: N
authors.lastname: Inui
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Funai
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shinmura
authors.forename: Takafumi
authors.initials: T
authors.lastname: Suda
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D046888:Tissue Array Analysis