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Detection of lung adenocarcinoma with ROS1 rearrangement by IHC, FISH, and RT-PCR and analysis of its clinicopathologic features

Authors Cao B, Wei P, Liu Z, Bi R, Lu Y, Zhang L, Zhang J, Yang Y, Shen C, Du X, Zhou X

Received 23 August 2015

Accepted for publication 18 November 2015

Published 31 December 2015 Volume 2016:9 Pages 131—138


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ram Prasad

Peer reviewer comments 3

Editor who approved publication: Professor Daniele Santini

Bing Cao,1–3,* Ping Wei,1–3,* Zebing Liu,4 Rui Bi,1–3 Yongming Lu,1–3 Ling Zhang,1–3 Jing Zhang,1–3 Yusi Yang,1–3 Chen Shen,1–3 Xiang Du,1–3 Xiaoyan Zhou1–3

1Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, 3Institute of Pathology, Fudan University, Shanghai, People’s Republic of China; 4Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

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.
Conclusion: 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.

Keywords: ROS1, lung adenocarcinoma, rearrangement, IHC, FISH, RT-PCR

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