ROS1 immunohistochemistry among major genotypes of non-small-cell lung cancer.

Abstract:

BACKGROUND:ROS1 gene fusions cause several cancers by constitutively activating the ROS1 tyrosine kinase receptor. ROS1-targeted inhibitor therapy improves survival in the approximately 1% to 2% of patients with lung adenocarcinoma with ROS1 gene fusions. Although fluorescence in situ hybridization (FISH) is the standard diagnostic procedure for detecting ROS1 rearrangements, we studied immunohistochemistry (IHC). MATERIALS AND METHODS:ROS1 IHC was performed on a selected cohort of 33 lung adenocarcinoma whole tissue specimens with alterations in the EGFR (n = 5), KRAS (n = 5), ERBB2 (HER2) (n = 3), ROS1 (n = 6), ALK (n = 5), and RET (n = 3) genes and pan-negative (n = 6) detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and FISH. RESULTS:In the cohort of 33 specimens, both ROS1 gene fusion using RT-PCR and high ROS1 protein expression using IHC were detected in 6 specimens. Of these 6 specimens, 5 were also positive by FISH for ROS1 gene rearrangements. All 27 lung cancer specimens that were negative for ROS1 rearrangements by genetic testing had no to low ROS1 protein expression. CONCLUSION:We have optimized ROS1 IHC and scoring to provide high sensitivity and specificity for detecting ROS1 gene rearrangements in whole tissue. ROS1 IHC could be a practical and cost-effective method to screen for ROS1 gene rearrangements.

journal_name

Clin Lung Cancer

journal_title

Clinical lung cancer

authors

Boyle TA,Masago K,Ellison KE,Yatabe Y,Hirsch FR

doi

10.1016/j.cllc.2014.10.003

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

106-11

issue

2

eissn

1525-7304

issn

1938-0690

pii

S1525-7304(14)00232-0

journal_volume

16

pub_type

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