Screening for ROS1 gene rearrangements in non-small-cell lung cancers using immunohistochemistry with FISH confirmation is an effective method to identify this rare target.

Selinger, CI; Li, BT; Pavlakis, N; Links, M; Gill, AJ; Lee, A; Clarke, S; Tran, TN; Lum, T; Yip, PY; Horvath, L; Yu, B; Kohonen-Corish, MRJ; O'Toole, SA; Cooper, WA

Screening for ROS1 gene rearrangements in non-small-cell lung cancers using immunohistochemistry with FISH confirmation is an effective method to identify this rare target.

Selinger, CI Li, BT Pavlakis, N Links, M Gill, AJ Lee, A Clarke, S Tran, TN Lum, T Yip, PY Horvath, L Yu, B Kohonen-Corish, MRJ O'Toole, SA Cooper, WA

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Publisher:: WILEY
Publication Type:: Journal Article
Citation:: Histopathology, 2017, 70, (3), pp. 402-411
Issue Date:: 2017-02

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Field	Value	Language
dc.contributor.author	Selinger, CI
dc.contributor.author	Li, BT
dc.contributor.author	Pavlakis, N
dc.contributor.author	Links, M
dc.contributor.author	Gill, AJ
dc.contributor.author	Lee, A
dc.contributor.author	Clarke, S
dc.contributor.author	Tran, TN
dc.contributor.author	Lum, T
dc.contributor.author	Yip, PY
dc.contributor.author	Horvath, L
dc.contributor.author	Yu, B
dc.contributor.author	Kohonen-Corish, MRJ
dc.contributor.author	O'Toole, SA
dc.contributor.author	Cooper, WA
dc.date.accessioned	2022-10-03T21:34:20Z
dc.date.available	2016-09-02
dc.date.available	2022-10-03T21:34:20Z
dc.date.issued	2017-02
dc.identifier.citation	Histopathology, 2017, 70, (3), pp. 402-411
dc.identifier.issn	0309-0167
dc.identifier.issn	1365-2559
dc.identifier.uri	http://hdl.handle.net/10453/162258
dc.description.abstract	AIMS: To assess the prevalence of ROS1 rearrangements in a retrospective and prospective diagnostic Australian cohort and evaluate the effectiveness of immunohistochemical screening. METHODS AND RESULTS: A retrospective cohort of 278 early stage lung adenocarcinomas and an additional 104 prospective non-small-cell lung cancer (NSCLC) cases referred for routine molecular testing were evaluated. ROS1 immunohistochemistry (IHC) was performed (D4D6 clone, Cell Signaling Technology) on all cases as well as fluorescence in-situ hybridization (FISH) using the ZytoVision and Abbott Molecular ROS1 FISH probes, with ≥15% of cells with split signals considered positive for rearrangement. Eighty-eight cases (32%) from the retrospective cohort showed staining by ROS1 IHC, and one case (0.4%) showed ROS1 rearrangement by FISH. Nineteen of the prospective diagnostic cases showed ROS1 IHC staining, 12 (12%) cases of which were confirmed as ROS1 rearranged by FISH. There were no ROS1 rearranged cases that showed no expression of ROS1 with IHC. The ROS1 rearranged cases in the prospective cohort were all EGFR wild-type and anaplastic lymphoma kinase (ALK) rearrangement-negative. The sensitivity of ROS1 IHC in the retrospective cohort was 100% and specificity was 76%. CONCLUSIONS: ROS1 rearrangements are rare events in lung adenocarcinomas. Selection of cases for ROS1 FISH testing, by excluding EGFR/ALK-positive cases and use of IHC to screen for potentially positive cases, can be used to enrich for the likelihood of identifying a ROS1 rearranged lung cancer and prevent the need to undertake expensive and time-consuming FISH testing in all cases.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	WILEY
dc.relation.ispartof	Histopathology
dc.relation.isbasedon	10.1111/his.13076
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1103 Clinical Sciences
dc.subject.classification	Pathology
dc.subject.mesh	Adult
dc.subject.mesh	Aged
dc.subject.mesh	Aged, 80 and over
dc.subject.mesh	Biomarkers, Tumor
dc.subject.mesh	Carcinoma, Non-Small-Cell Lung
dc.subject.mesh	Female
dc.subject.mesh	Gene Rearrangement
dc.subject.mesh	Humans
dc.subject.mesh	Immunohistochemistry
dc.subject.mesh	In Situ Hybridization, Fluorescence
dc.subject.mesh	Lung Neoplasms
dc.subject.mesh	Male
dc.subject.mesh	Middle Aged
dc.subject.mesh	Protein-Tyrosine Kinases
dc.subject.mesh	Proto-Oncogene Proteins
dc.subject.mesh	Humans
dc.subject.mesh	Carcinoma, Non-Small-Cell Lung
dc.subject.mesh	Lung Neoplasms
dc.subject.mesh	Proto-Oncogene Proteins
dc.subject.mesh	Immunohistochemistry
dc.subject.mesh	In Situ Hybridization, Fluorescence
dc.subject.mesh	Gene Rearrangement
dc.subject.mesh	Adult
dc.subject.mesh	Aged
dc.subject.mesh	Aged, 80 and over
dc.subject.mesh	Middle Aged
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Protein-Tyrosine Kinases
dc.subject.mesh	Biomarkers, Tumor
dc.title	Screening for ROS1 gene rearrangements in non-small-cell lung cancers using immunohistochemistry with FISH confirmation is an effective method to identify this rare target.
dc.type	Journal Article
utslib.citation.volume	70
utslib.location.activity	England
utslib.for	1103 Clinical Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
utslib.copyright.status	closed_access	*
dc.date.updated	2022-10-03T21:34:18Z
pubs.issue	3
pubs.publication-status	Published
pubs.volume	70
utslib.citation.issue	3

Abstract:

AIMS: To assess the prevalence of ROS1 rearrangements in a retrospective and prospective diagnostic Australian cohort and evaluate the effectiveness of immunohistochemical screening. METHODS AND RESULTS: A retrospective cohort of 278 early stage lung adenocarcinomas and an additional 104 prospective non-small-cell lung cancer (NSCLC) cases referred for routine molecular testing were evaluated. ROS1 immunohistochemistry (IHC) was performed (D4D6 clone, Cell Signaling Technology) on all cases as well as fluorescence in-situ hybridization (FISH) using the ZytoVision and Abbott Molecular ROS1 FISH probes, with ≥15% of cells with split signals considered positive for rearrangement. Eighty-eight cases (32%) from the retrospective cohort showed staining by ROS1 IHC, and one case (0.4%) showed ROS1 rearrangement by FISH. Nineteen of the prospective diagnostic cases showed ROS1 IHC staining, 12 (12%) cases of which were confirmed as ROS1 rearranged by FISH. There were no ROS1 rearranged cases that showed no expression of ROS1 with IHC. The ROS1 rearranged cases in the prospective cohort were all EGFR wild-type and anaplastic lymphoma kinase (ALK) rearrangement-negative. The sensitivity of ROS1 IHC in the retrospective cohort was 100% and specificity was 76%. CONCLUSIONS: ROS1 rearrangements are rare events in lung adenocarcinomas. Selection of cases for ROS1 FISH testing, by excluding EGFR/ALK-positive cases and use of IHC to screen for potentially positive cases, can be used to enrich for the likelihood of identifying a ROS1 rearranged lung cancer and prevent the need to undertake expensive and time-consuming FISH testing in all cases.

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http://hdl.handle.net/10453/162258