title: Detection of lung adenocarcinoma with ROS1 rearrangement by IHC, FISH, and RT-PCR and analysis of its clinicopathologic features.
abstract: OBJECTIVE
  To detect ROS1 rearrangement using three different assays, including immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and reverse transcription polymerase chain reaction (RT-PCR), and to analyze the clinicopathologic features of ROS1 rearrangement in patients with lung adenocarcinoma.
  
  
  METHODS
  One hundred eighty-three consecutive patients with lung adenocarcinoma with operation and follow-up data were analyzed for ROS1 rearrangement by IHC, FISH, and RT-PCR. PCR products of the RT-PCR-positive samples were sequenced for confirmation of the specific fusion partners.
  
  
  RESULTS
  Three of the 183 (1.64%) cases were identified to be positive for ROS1 rearrangement through all three methods. The fusion patterns were CD74 e6-ROS1 e32, CD74 e6-ROS1 e34, and TPM3 e8-ROS1 e35, respectively. FISH-positive cases showed two types of signals, single 3' signals (green) and split red and green signals. Using FISH as a standard method, the sensitivity and specificity of ROS1 IHC with 1+ staining or more were 100% and 96.67%, respectively. The sensitivity and specificity of RT-PCR were both 100%. Univariate analysis identified female sex (P=0.044), Stage I disease (P<0.001), and ROS1-negative status (P=0.022) to be significantly associated with longer overall survival.
  
  
  CONCLUSIONS
  IHC, FISH, and RT-PCR are all effective methods for the detection of ROS1 rearrangement. IHC would be a useful screening method in routine pathologic laboratories. RT-PCR can detect exact fusion patterns. ROS1 rearrangement may be a worse prognostic factor. The exact correlation of ROS1 rearrangement with prognosis and whether different fusion types are correlated with different responses to targeted therapy need to be further investigated.
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; Institute of Pathology, Fudan University, Shanghai, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Cao
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; Institute of Pathology, Fudan University, Shanghai, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.affiliation: Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Zebing
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; Institute of Pathology, Fudan University, Shanghai, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Bi
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; Institute of Pathology, Fudan University, Shanghai, People's Republic of China.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; Institute of Pathology, Fudan University, Shanghai, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; Institute of Pathology, Fudan University, Shanghai, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; Institute of Pathology, Fudan University, Shanghai, People's Republic of China.
authors.forename: Yusi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; Institute of Pathology, Fudan University, Shanghai, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; Institute of Pathology, Fudan University, Shanghai, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; Institute of Pathology, Fudan University, Shanghai, People's Republic of China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhou
keywords: FISH; IHC; ROS1; RT-PCR; lung adenocarcinoma; rearrangement