title: Prevalence and clinicopathological characteristics of ALK fusion subtypes in lung adenocarcinomas from Chinese populations.
abstract: OBJECTIVE
  We performed this retrospective study to have a comprehensive investigation of the clinicopathological characteristics of ALK fusion-positive lung adenocarcinoma in Chinese populations.
  
  
  METHODS
  We screened 1407 patients with primary lung adenocarcinoma from October 2007 to May 2013. Quantitative real-time PCR (qRT-PCR), reverse transcriptase PCR (RT-PCR), and fluorescence in situ hybridization were performed to detect ALK fusion genes, with validation of positive results using immunohistochemistry. Clinicopathological characteristics were collected to assess prognosis in ALK fusion-positive patients.
  
  
  RESULTS
  Of 1407 patients with lung adenocarcinoma, there were 74 (5.3 %) ALK fusion-positive patients. Patients harboring ALK fusion were significantly younger (56.0 years vs. 59.8 years p = 0.002) and were more likely to have advanced stages (stage III or stage IV) (OR 1.761; 95 % CI 1.10-2.82, p = 0.017). Lepidic predominant adenocarcinoma was rarely found in ALK fusion patients (2.7 vs. 13.5 % p = 0.025), while IMA (invasive mucinous adenocarcinoma) predominant adenocarcinoma was more frequently found (21.6 vs. 5.0 % p < 0.001). ALK fusion was neither a risk factor nor protective factor in relapse-free survival and overall survival. Male, current smoker, and EML4-ALK variant 3 indicated poor prognosis among ALK fusion-positive lung adenocarcinomas.
  
  
  CONCLUSIONS
  ALK fusion was detected in 5.3 % (74/1407) of the Chinese patients with lung adenocarcinoma. ALK fusion defines a molecular subset of lung adenocarcinoma with unique clinicopathological characteristics. Different ALK fusion variants determine distinct prognoses.
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Difan
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Yunjian
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Shanbo
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Ranxia
authors.initials: R
authors.lastname: Gong
authors.affiliation: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
authors.forename: Xuxia
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China. Sun_yihua76@hotmail.com.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. Sun_yihua76@hotmail.com.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China. hqchen1@yahoo.com.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. hqchen1@yahoo.com.|Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. hqchen1@yahoo.com.|Institutes of Biomedical Sciences, Fudan University, 130 Dong-An Road, Shanghai, 200032, China. hqchen1@yahoo.com.
authors.forename: Haiquan
authors.initials: H
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D044466:Asian People / Q000235:genetics / Q000706:statistics & numerical data*; D002681:China / Q000453:epidemiology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000737:chemistry / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000209:etiology; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000032:analysis* / Q000235:genetics*; D011237:Predictive Value of Tests; D015995:Prevalence; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000032:analysis / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000032:analysis / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000032:analysis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D016019:Survival Analysis
chemical_list: D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D048493:Proto-Oncogene Proteins B-raf; D051096:Proto-Oncogene Proteins c-ret; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C522504:EML4-ALK fusion protein, human; C117307:KRAS protein, human; C000626173:ALK protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C099282:RET protein, human; C062333:ROS1 protein, human; C482119:BRAF protein, human
keywords: ALK; Lung adenocarcinoma; Prognosis; Subtypes