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

被引:65
作者
Kim, Min Hwan [1 ]
Shim, Hyo Sup [2 ]
Kang, Dae Ryong [3 ]
Jung, Ji Ye [4 ]
Lee, Chang Young [5 ]
Kim, Dae Joon [5 ]
Lee, Jin Gu [5 ]
Bae, Mi Kyung [5 ]
Kim, Hye Ryun [1 ]
Lim, Sun Min [1 ]
Kim, Eun Young [4 ]
Park, Ji Soo [1 ]
Chung, Kyung Young [5 ]
Kim, Hyun-Jung [6 ]
Kim, Joo Hang [1 ]
Cho, Byoung Chul [1 ]
机构
[1] Yonsei Univ, Coll Med, Yonsei Canc Ctr, Div Med Oncol,Dept Internal Med,Severance Hosp, Seoul 120752, South Korea
[2] Yonsei Univ, Coll Med, Severance Hosp, Dept Pathol, Seoul 120752, South Korea
[3] Yonsei Univ, Coll Med, Severance Hosp, Biostat Collaborat Unit, Seoul 120752, South Korea
[4] Yonsei Univ, Coll Med, Severance Hosp, Div Pulmonol,Dept Internal Med, Seoul 120752, South Korea
[5] Yonsei Univ, Coll Med, Severance Hosp, Dept Thorac & Cardiovasc Surg, Seoul 120752, South Korea
[6] JEUK Co Ltd, JEUK Inst Canc Res, Gumi, Kyungbuk, South Korea
关键词
Anaplastic lymphoma kinase; C-roe oncogene 1; Prognosis; Never-smokers; Lung adenocarcinoma; HARBORING EML4-ALK; CANCER; MUTATIONS; FUSION; INHIBITION; GEFITINIB; ONCOGENE; SURVIVAL; FEATURES; GENE;
D O I
10.1016/j.lungcan.2014.01.003
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objectives: The aim of this study is to evaluate the prevalence and prognostic significance of anaplastic lymphoma kinase (ALK) and c-ros oncogene I (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 ofALK or ROS1 fusion-positive lung adenocarcinoma in never-smokers after curative surgery. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:389 / 395
页数:7
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