TY - JOUR
T1 - ROS1 fusions in resected stage I-III adenocarcinoma
T2 - Results from the European Thoracic Oncology Platform Lungscape project
AU - Speel, Ernst Jan M.
AU - Dafni, Urania
AU - for the Lungscape Consortium
AU - Thunnissen, Erik
AU - Hendrik Rüschoff, Jan
AU - O'Brien, Cathal
AU - Kowalski, Jacek
AU - Kerr, Keith M.
AU - Bubendorf, Lukas
AU - Sansano, Irene
AU - Joseph, Leena
AU - Kriegsmann, Mark
AU - Navarro, Atilio
AU - Monkhorst, Kim
AU - Bille Madsen, Line
AU - Hernandez Losa, Javier
AU - Biernat, Wojciech
AU - Stenzinger, Albrecht
AU - Rüland, Andrea
AU - Hillen, Lisa M.
AU - Marti, Nesa
AU - Molina-Vila, Miguel A.
AU - Dellaporta, Tereza
AU - Kammler, Roswitha
AU - Peters, Solange
AU - Stahel, Rolf A.
AU - Finn, Stephen P.
AU - Radonic, Teodora
N1 - Publisher Copyright:
© 2024 Elsevier B.V.
PY - 2024/8
Y1 - 2024/8
N2 - Background: ROS1 fusion is a relatively low prevalence (0.6–2.0%) but targetable driver in lung adenocarcinoma (LUAD). Robust and low-cost tests, such as immunohistochemistry (IHC), are desirable to screen for patients potentially harboring this fusion. The aim was to investigate the prevalence of ROS1 fusions in a clinically annotated European stage I-III LUAD cohort using IHC screening with the in vitro diagnostics (IVD)-marked clone SP384, followed by confirmatory molecular analysis in pre-defined subsets. Methods: Resected LUADs constructed in tissue microarrays, were immunostained for ROS1 expression using SP384 clone in a ready-to-use kit and Ventana immunostainers. After external quality control, analysis was performed by trained pathologists. Staining intensity of at least 2+ (any percentage of tumor cells) was considered IHC positive (ROS1 IHC + ). Subsequently, ROS1 IHC + cases were 1:1:1 matched with IHC0 and IHC1 + cases and subjected to orthogonal ROS1 FISH and RNA-based testing.Results: The prevalence of positive ROS1 expression (ROS1 IHC + ), defined as IHC 2+/3+, was 4 % (35 of 866 LUADs). Twenty-eight ROS1 IHC + cases were analyzed by FISH/RNA-based testing, with only two harboring a confirmed ROS1 gene fusion, corresponding to a lower limit for the prevalence of ROS1 gene fusion of 0.23 %. They represent a 7 % probability of identifying a fusion among ROS1 IHC + cases. Both confirmed cases were among the only four with sufficient material and H-score ≥ 200, leading to a 50 % probability of identifying a ROS1 gene fusion in cases with an H-score considered strongly positive. All matched ROS1 IHC- (IHC0 and IHC1 + ) cases were also found negative by FISH/RNA-based testing, leading to a 100 % probability of lack of ROS1 fusion for ROS1 IHC- cases. Conclusions: The prevalence of ROS1 fusion in an LUAD stage I-III European cohort was relatively low. ROS1 IHC using SP384 clone is useful for exclusion of ROS1 gene fusion negative cases.
AB - Background: ROS1 fusion is a relatively low prevalence (0.6–2.0%) but targetable driver in lung adenocarcinoma (LUAD). Robust and low-cost tests, such as immunohistochemistry (IHC), are desirable to screen for patients potentially harboring this fusion. The aim was to investigate the prevalence of ROS1 fusions in a clinically annotated European stage I-III LUAD cohort using IHC screening with the in vitro diagnostics (IVD)-marked clone SP384, followed by confirmatory molecular analysis in pre-defined subsets. Methods: Resected LUADs constructed in tissue microarrays, were immunostained for ROS1 expression using SP384 clone in a ready-to-use kit and Ventana immunostainers. After external quality control, analysis was performed by trained pathologists. Staining intensity of at least 2+ (any percentage of tumor cells) was considered IHC positive (ROS1 IHC + ). Subsequently, ROS1 IHC + cases were 1:1:1 matched with IHC0 and IHC1 + cases and subjected to orthogonal ROS1 FISH and RNA-based testing.Results: The prevalence of positive ROS1 expression (ROS1 IHC + ), defined as IHC 2+/3+, was 4 % (35 of 866 LUADs). Twenty-eight ROS1 IHC + cases were analyzed by FISH/RNA-based testing, with only two harboring a confirmed ROS1 gene fusion, corresponding to a lower limit for the prevalence of ROS1 gene fusion of 0.23 %. They represent a 7 % probability of identifying a fusion among ROS1 IHC + cases. Both confirmed cases were among the only four with sufficient material and H-score ≥ 200, leading to a 50 % probability of identifying a ROS1 gene fusion in cases with an H-score considered strongly positive. All matched ROS1 IHC- (IHC0 and IHC1 + ) cases were also found negative by FISH/RNA-based testing, leading to a 100 % probability of lack of ROS1 fusion for ROS1 IHC- cases. Conclusions: The prevalence of ROS1 fusion in an LUAD stage I-III European cohort was relatively low. ROS1 IHC using SP384 clone is useful for exclusion of ROS1 gene fusion negative cases.
UR - http://www.scopus.com/inward/record.url?scp=85198067981&partnerID=8YFLogxK
U2 - 10.1016/j.lungcan.2024.107860
DO - 10.1016/j.lungcan.2024.107860
M3 - Article
C2 - 39002492
AN - SCOPUS:85198067981
SN - 0169-5002
VL - 194
JO - Lung Cancer
JF - Lung Cancer
M1 - 107860
ER -
