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Clinical and prognostic implications of ALK and ROS1 rearrangements in never-smokers with surgically resected lung adenocarcinoma

 Min Hwan Kim  ;  Hyo Sup Shim  ;  Dae Ryong Kang  ;  Ji Ye Jung  ;  Chang Young Lee  ;  Dae Joon Kim  ;  Jin Gu Lee  ;  Mi Kyung Bae  ;  Hye Ryun Kim  ;  Sun Min Lim  ;  Eun Young Kim  ;  Ji Soo Park  ;  Kyung Young Chung  ;  Hyun-Jung Kim  ;  Joo Hang Kim  ;  Byoung Chul Cho 
 LUNG CANCER, Vol.83(3) : 389-395, 2014 
Journal Title
Issue Date
Adenocarcinoma/diagnosis* ; Adenocarcinoma/genetics ; Adenocarcinoma/mortality* ; DNA Mutational Analysis ; Gene Rearrangement/genetics ; Lung Neoplasms/diagnosis* ; Lung Neoplasms/genetics ; Lung Neoplasms/mortality ; Mutation/genetics ; Neoplasm Staging ; Pneumonectomy ; Protein-Tyrosine Kinases/genetics* ; Proto-Oncogene Proteins/genetics* ; Proto-Oncogene Proteins p21(ras) ; Receptor Protein-Tyrosine Kinases/genetics* ; Receptor, Epidermal Growth Factor/genetics ; Recurrence ; Retrospective Studies ; Smoking ; Survival Analysis ; ras Proteins/genetics
Anaplastic lymphoma kinase ; C-ros oncogene 1 ; Lung adenocarcinoma ; Never-smokers ; Prognosis
OBJECTIVES: The aim of this study is to evaluate the prevalence and prognostic significance of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) rearrangement in never-smokers with surgically resected lung adenocarcinoma. METHODS: We retrospectively analyzed 162 consecutive never-smokers who underwent curative resection for stage IB to IIIA lung adenocarcinoma at a single institution. We concurrently analyzed mutations in the epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) genes, and investigated ALK rearrangements by fluorescence in situ hybridization assay. ROS1 rearrangement was also determined in all triple (EGFR/KRAS/ALK)-negative tumors. RESULTS: Of 162 never smokers with lung adenocarcinoma, 14 (8.6%) and 5 (3.1%) had ALK and ROS1 rearrangements, respectively. Nineteen of the 74 (25.7%) EGFR and KRAS mutation-negative patients were fusion-positive (ALK or ROS1 fusion). Fusion-positive patients tended to have shorter median disease-free survival (DFS) than fusion-negative patients (28.0 vs. 33.9 months; p=0.128). In multivariate analysis, fusion-positive patients had significantly poorer DFS than fusion-negative patients after adjustment for age, sex, T stage, N stage, and adjuvant chemotherapy use (p=0.022; hazard ratio, 2.11; 95% confidence interval, 1.19-4.30). The first recurrence sites were not significantly different between fusion-positive and fusion-negative patients in this study. CONCLUSION: This study shows significantly poorer DFS of ALK or ROS1 fusion-positive lung adenocarcinoma in never-smokers after curative surgery.
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Appears in Collections:
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 Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Dae Joon(김대준)
Kim, Min Hwan(김민환) ORCID logo https://orcid.org/0000-0002-1595-6342
Kim, Eun Young(김은영) ORCID logo https://orcid.org/0000-0002-3281-5744
Kim, Joo Hang(김주항)
Kim, Hyun Jeong(김현정)
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Park, Ji Soo(박지수) ORCID logo https://orcid.org/0000-0002-0023-7740
Bae, Mi Kyung(배미경)
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Lee, Jin Gu(이진구)
Lee, Chang Young(이창영)
Lim, Sun Min(임선민)
Chung, Kyung Young(정경영)
Jung, Ji Ye(정지예) ORCID logo https://orcid.org/0000-0003-1589-4142
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
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