Screening of ROS1 rearrangements in lung adenocarcinoma by immunohistochemistry and comparison with ALK rearrangements

Yoon Jin Cha, Jae Seok Lee, Hye Ryun Kim, Sun Min Lim, Byoung Chul Cho, Chang Young Lee, Hyo Sup Shim

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

ROS1 rearrangement is a predictive biomarker for response to the tyrosine kinase inhibitor, crizotinib. We investigated the usefulness of ROS1 immunohistochemistry (IHC) for the detection of patients who harbor ROS1 rearrangements in two separate cohorts. We also compared ROS1 IHC with ALK IHC in terms of diagnostic performance to predict each gene rearrangement. In a retrospective cohort, IHC was performed in 219 cases of lung adenocarcinoma with already known genetic alterations. In a prospective cohort, we performed IHC for 111 consecutive cases of lung adenocarcinoma and confirmed the results by subsequent FISH. In the retrospective cohort, all 8 ROS1-rearranged tumors were immunoreactive, and 14 of 211 ROS1-wild cases were immunoreactive (sensitivity 100% and specificity 93.4%). In the prospective cohort, all IHC-negative cases were FISH-negative, and 5 of 34 ROS1 immunoreactive cases were ROS1-rearranged (sensitivity 100% and specificity 72.6%). In ROS1-wild tumors, ROS1 protein was more expressed in the tumors of ever-smokers than in those of never-smokers (p = 0.003). ALK IHC showed 100% sensitivity and 98.1 to 100% specificity in both patient cohorts. In conclusion, ROS1 IHC is highly sensitive, but less specific compared with ALK IHC for detection of the corresponding rearrangement. ROS1 IHC-reactive tumors, especially when the tumor is stained with moderate to strong intensity or a diffuse pattern, are recommended to undergo FISH to confirm the gene rearrangement.

Original languageEnglish
Article numbere103333
JournalPloS one
Volume9
Issue number7
DOIs
Publication statusPublished - 2014 Jul 24

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adenocarcinoma
immunohistochemistry
Screening
Immunohistochemistry
lungs
screening
Tumors
neoplasms
Gene Rearrangement
Neoplasms
Genes
Adenocarcinoma of lung
Sensitivity and Specificity
Biomarkers
Ports and harbors
Protein-Tyrosine Kinases
tyrosine
biomarkers
phosphotransferases (kinases)
genes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Cha, Yoon Jin ; Lee, Jae Seok ; Kim, Hye Ryun ; Lim, Sun Min ; Cho, Byoung Chul ; Lee, Chang Young ; Shim, Hyo Sup. / Screening of ROS1 rearrangements in lung adenocarcinoma by immunohistochemistry and comparison with ALK rearrangements. In: PloS one. 2014 ; Vol. 9, No. 7.
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abstract = "ROS1 rearrangement is a predictive biomarker for response to the tyrosine kinase inhibitor, crizotinib. We investigated the usefulness of ROS1 immunohistochemistry (IHC) for the detection of patients who harbor ROS1 rearrangements in two separate cohorts. We also compared ROS1 IHC with ALK IHC in terms of diagnostic performance to predict each gene rearrangement. In a retrospective cohort, IHC was performed in 219 cases of lung adenocarcinoma with already known genetic alterations. In a prospective cohort, we performed IHC for 111 consecutive cases of lung adenocarcinoma and confirmed the results by subsequent FISH. In the retrospective cohort, all 8 ROS1-rearranged tumors were immunoreactive, and 14 of 211 ROS1-wild cases were immunoreactive (sensitivity 100{\%} and specificity 93.4{\%}). In the prospective cohort, all IHC-negative cases were FISH-negative, and 5 of 34 ROS1 immunoreactive cases were ROS1-rearranged (sensitivity 100{\%} and specificity 72.6{\%}). In ROS1-wild tumors, ROS1 protein was more expressed in the tumors of ever-smokers than in those of never-smokers (p = 0.003). ALK IHC showed 100{\%} sensitivity and 98.1 to 100{\%} specificity in both patient cohorts. In conclusion, ROS1 IHC is highly sensitive, but less specific compared with ALK IHC for detection of the corresponding rearrangement. ROS1 IHC-reactive tumors, especially when the tumor is stained with moderate to strong intensity or a diffuse pattern, are recommended to undergo FISH to confirm the gene rearrangement.",
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Screening of ROS1 rearrangements in lung adenocarcinoma by immunohistochemistry and comparison with ALK rearrangements. / Cha, Yoon Jin; Lee, Jae Seok; Kim, Hye Ryun; Lim, Sun Min; Cho, Byoung Chul; Lee, Chang Young; Shim, Hyo Sup.

In: PloS one, Vol. 9, No. 7, e103333, 24.07.2014.

Research output: Contribution to journalArticle

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