Scientific publications

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Non-Small Cell Lung Carcinoma Patients: the ROSING Study

Jul 23, 2019 | Magazine: Journal of Thoracic Oncology

Conde E (1), Hernandez S (2), Martinez R (2), Angulo B (1), De Castro J (3), Collazo-Lorduy A (2), Jimenez B (2), Muriel A (4), Mate JL (5), Moran T (6), Aranda I (7), Massuti B (7), Rojo F (8), Domine M (9), Sansano I (10), Garcia F (11), Felip E (10), Mancheño N (12), Juan O (12), Sanz J (13), Gonzalez-Larriba JL (13), Atienza-Cuevas L (14), Arriola-Arellano E (14), Abdulkader I (15), Garcia-Gonzalez J (15), Camacho C (16), Rodriguez-Abreu D (16), Teixido C (17), Reguart N (17), Gonzalez-Piñeiro A (18), Lazaro-Quintela M (18), Lozano MD (19), Gurpide A (19), Gomez-Roman J (20), Lopez-Brea M (20), Pijuan L (21), Salido M (21), Arriola E (21), Company A (22), Insa A (22), Esteban-Rodriguez I (3), Saiz M (23), Azkona E (23), Alvarez R (24), Artal A (24), Plaza ML (25), Aguiar D (25), Enguita AB (26), Benito A (27), Paz-Ares L (28), Garrido P (29), Lopez-Rios F (30)

(1) Hospital Universitario HM Sanchinarro-CIBERONC, Madrid. Spain.
(2) Hospital Universitario HM Sanchinarro, Madrid. Spain.
(3) Hospital Universitario La Paz, Madrid. Spain.
(4) Hospital Universitario Ramon y Cajal, IRYCIS and CIBERESP, Madrid. Spain.
(5) Hospital Universitari Germans Trias i Pujol, Badalona. Spain.
(6) Instituto Catalan de Oncologia-Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), Badalona-Apllied Research Group of Oncology (B-ARGO), Badalona. Spain.
(7) Hospital General Universitario-ISABIAL, Alicante. Spain.
(8) Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz-CIBERONC, Madrid. Spain.
(9) Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz, Madrid. Spain.
(10) Hospital Universitari Vall d'Hebron, Barcelona. Spain.
(11) Hospital Quironsalud, Barcelona. Spain.
(12) Hospital Universitario La Fe, Valencia. Spain.
(13) Hospital Clinico Universitario San Carlos, Madrid. Spain.
(14) Hospital Universitario Puerta del Mar, Cadiz. Spain.
(15) Hospital Clinico Universitario de Santiago, Santiago De Compostela.
(16) Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas De Gran Canaria. Spain.
(17) Hospital Clinic, Barcelona. Spain.
(18) Hospital Alvaro Cunqueiro, Vigo. Spain.
(19) Clinica Universidad de Navarra, Pamplona. Spain.
(20) Hospital Universitario Marques de Valdecilla, Santander. Spain.
(21) Hospital del Mar, Barcelona. Spain.
(22) Hospital Clinico Universitario, Valencia. Spain.
(23) Hospital Universitario de Cruces, Baracaldo. Spain.
(24) Hospital Universitario Miguel Servet, Zaragoza. Spain.
(25) Hospital Universitario de Gran Canaria Doctor Negrin, Las Palmas de Gran Canaria. Spain.
(26) Hospital Universitario 12 de Octubre, Madrid. Spain.
(27) Hospital Universitario Ramon y Cajal, Madrid. Spain.
(28) Hospital Universitario 12 de Octubre-CIBERONC, Madrid. Spain.
(29) Hospital Universitario Ramon y Cajal-CIBERONC, Madrid. Spain.
(30) Hospital Universitario HM Sanchinarro-CIBERONC, Madrid. Spain.


The ROS1 gene rearrangement has become an important biomarker in non-small cell lung carcinomas (NSCLCs). The CAP/IASLC/AMP testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data.


Forty-three ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana) and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (OncomineTM Dx, Thermo Fisher Scientific).


An H-score of ≥150 or the presence of ≥70% of ≥2+ stained tumor cells by SP384 clone were the optimal cut-off value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results with an H-score of ≥100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent using the SP384 clone (P < 0.0001). EZR-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (P = 0.001 and P = 0.017, respectively).


The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm.

CITATION  J Thorac Oncol. 2019 Jul 23. pii: S1556-0864(19)30562-3. doi: 10.1016/j.jtho.2019.07.005