title: ALK, ROS1 and RET fusions in 1139 lung adenocarcinomas: a comprehensive study of common and fusion pattern-specific clinicopathologic, histologic and cytologic features.
abstract: BACKGROUND
  To have a comprehensive investigation of the clinicopathologic, histologic and cytologic features of fusion-positive lung adenocarcinomas.
  
  
  METHODS
  Quantitative real-time reverse transcriptase PCR (qRT-PCR) and reverse transcriptase PCR (RT-PCR) were simultaneously performed to screen ALK, ROS1 and RET fusions in resected tumor samples from 1139 Chinese lung adenocarcinoma patients, with validation of positive results using fluorescent in situ hybridization. Clinicopathologic characteristics, predominant histologic subtype and cytomorphology were assessed in fusion-positive lung adenocarcinomas and compared to those harboring EGFR, KRAS, HER2 or BRAF mutations.
  
  
  RESULTS
  There were 58 (5.1%) ALK fusions, 11 (1.0%) ROS1 fusions and 15 (1.3%) RET fusions. Tumors with ROS1 fusions had significantly larger diameter than ROS1 fusion-negative tumors (P = 0.007), whereas all the 15 tumors harboring RET fusions were ≤ 3 cm in diameter (P = 0.001). The three fusion genes were all more prevalent in solid-predominant adenocarcinoma. Compared to fusion-negative lung adenocarcinomas, tumors harboring a fusion gene had significantly higher prevalence of extracellular mucin (P < 0.001), cribriform pattern (P < 0.001), signet ring cells (P < 0.001) and hepatoid cytology (P < 0.001). No significant difference in relapse-free survival (P = 0.147) and overall survival (P = 0.444) was observed between fusion-positive and fusion-negative patients.
  
  
  CONCLUSIONS
  This study showed fusion-positive lung adenocarcinomas had identifiable common and fusion-pattern specific clinicopathologic, histologic and cytologic features, offering implications for fusion genes screening.
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 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: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 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 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 Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Haichuan
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 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, 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, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Ye
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Yiliang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Deng
authors.initials: D
authors.lastname: Cai
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: Lei
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: Sun_yihua76@hotmail.com.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: hqchen@yahoo.com.
authors.forename: Haiquan
authors.initials: H
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000077548:Anaplastic Lymphoma Kinase; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
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; D018631:ras Proteins; 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 fusions; Cytomorphology; Histology; Lung adenocarcinoma; RET fusions; ROS1 fusions