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Fibroblast Growth Factor Receptor 1 Gene Amplification Is Associated With Poor Survival and Cigarette Smoking Dosage in Patients With Resected Squamous Cell Lung Cancer

Authors
 Hye Ryun Kim  ;  Dae Joon Kim  ;  Dae Ryong Kang  ;  Jin Gu Lee  ;  Sun Min Lim  ;  Chang Young Lee  ;  Sun Young Rha  ;  Mi Kyung Bae  ;  Young Joo Lee  ;  Se Hoon Kim  ;  Sang-Jun Ha  ;  Ross Andrew Soo  ;  Kyung Young Chung  ;  Joo Hang Kim  ;  Ji Hyun Lee  ;  Hyo Sup Shim  ;  Byoung Chul Cho 
Citation
 JOURNAL OF CLINICAL ONCOLOGY, Vol.31(6) : 731-737, 2013 
Journal Title
 JOURNAL OF CLINICAL ONCOLOGY 
ISSN
 0732-183X 
Issue Date
2013
MeSH
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell/drug therapy ; Carcinoma, Squamous Cell/genetics* ; Carcinoma, Squamous Cell/pathology ; Chemotherapy, Adjuvant ; Female ; Gene Amplification ; Gene Dosage ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Kaplan-Meier Estimate ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics* ; Lung Neoplasms/pathology ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Outcome Assessment (Health Care)/methods ; Outcome Assessment (Health Care)/statistics & numerical data ; Prognosis ; Proportional Hazards Models ; Receptor, Fibroblast Growth Factor, Type 1/genetics* ; Receptor, Fibroblast Growth Factor, Type 1/metabolism ; Smoking*
Keywords
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell/drug therapy ; Carcinoma, Squamous Cell/genetics* ; Carcinoma, Squamous Cell/pathology ; Chemotherapy, Adjuvant ; Female ; Gene Amplification ; Gene Dosage ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Kaplan-Meier Estimate ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics* ; Lung Neoplasms/pathology ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Outcome Assessment (Health Care)/methods ; Outcome Assessment (Health Care)/statistics & numerical data ; Prognosis ; Proportional Hazards Models ; Receptor, Fibroblast Growth Factor, Type 1/genetics* ; Receptor, Fibroblast Growth Factor, Type 1/metabolism ; Smoking*
Abstract
PURPOSE: To investigate the frequency and the prognostic role of fibroblast growth factor receptor 1 (FGFR1) amplification in patients with surgically resected squamous cell carcinoma of the lung (SCCL) and the association between smoking and FGFR1 amplification. PATIENTS AND METHODS: Gene copy number of FGFR1 was investigated in microarrayed tumors from 262 patients with SCCL who had tumor tissue as well as smoking and survival data available. Gene copy number was evaluated by fluorescent in situ hybridization, and an FGFR1-amplified tumor (FGFR1 amp(+)) was prespecified as a tumor with nine or more copies of FGFR1. RESULTS: Among 262 patients, the frequency of FGFR1 amp(+) was 13.0%. Patients with FGFR1 amp(+) had significantly shorter disease-free survival (DFS; 26.9 v 94.6 months; P < .001) as well as shorter overall survival (OS; 51.2 v 115.0 months; P = .002) than those without FGFR1 amp(+). Multivariate modeling confirmed that patients with FGFR1 amp(+) had a significantly greater risk of recurrence and death than those without FGFR1 amp(+) after adjusting for sex, smoking status, pathologic stage, and adjuvant chemotherapy (DFS: adjusted hazard ratio [AHR], 2.24; 95% CI, 1.45 to 3.45; P < .001; OS: AHR, 1.83; 95% CI, 1.15 to 2.89; P = .01). The frequency of FGFR1 amp(+) was significantly higher in current smokers than in former smokers and never-smokers (28.9% v 2.5% v 0%; P(trend) < .001). As the smoking dosage increased, so did the incidence of FGFR1 amp(+) (P(trend) = .002). CONCLUSION: FGFR1 amplification is an independent negative prognostic factor in surgically resected SCCL and is associated with cigarette smoking in a dose-dependent manner. FGFR1 amplification is a relevant therapeutic target in Asian patients with SCCL.
Full Text
http://jco.ascopubs.org/content/31/6/731.long
DOI
10.1200/JCO.2012.43.8622
Appears in Collections:
5. Research Institutes (연구소) > Research Center for Human Natural Defense System (생체방어연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Preventive Medicine and Public Health (예방의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Dae Ryong(강대용)
Kim, Dae Joon(김대준)
Kim, Se Hoon(김세훈) ORCID logo https://orcid.org/0000-0001-7516-7372
Kim, Joo Hang(김주항)
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Bae, Mi Kyung(배미경)
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Lee, Ji Hyun(이지현)
Lee, Jin Gu(이진구)
Lee, Chang Young(이창영)
Lim, Sun Min(임선민)
Chung, Kyung Young(정경영)
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/86471
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