Véronique Hofman1, Isabelle Rouquette2, Elodie Long-Mira1, Nicolas Piton3, Emmanuel Chamorey4, Simon Heeke5, Jean Michel Vignaud6, Clémence Yguel6, Julien Mazières7, Anne-Laure Lepage8, Frédéric Bibeau8, Hugues Begueret9, Sandra Lassalle10, Salomé Lalvée11, Katia Zahaf11, Jonathan Benzaquen12, Michel Poudenx13, Charles-Hugo Marquette13, Jean-Christophe Sabourin3, Marius Ilié1, Paul Hofman14. 1. Université Côte d'Azur, University Hospital Federation OncoAge, Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France; Université Côte d'Azur, CNRS, INSERM, Institute of Research on Cancer and Ageing of Nice (IRCAN), University Hospital Federation OncoAge, Nice, France; Université Côte d'Azur, University Hospital Federation OncoAge, Hospital-Related Biobank (BB-0033-00025), Pasteur Hospital, Nice, France. 2. CHU Toulouse, Department of Pathology, Toulouse, France. 3. Charles Nicolle Hospital, Department of Pathology, Rouen, France. 4. Antoine Lacassagne Comprehensive Cancer Center, Biostatistics Unit, Nice, France. 5. Université Côte d'Azur, CNRS, INSERM, Institute of Research on Cancer and Ageing of Nice (IRCAN), University Hospital Federation OncoAge, Nice, France. 6. CHU Nancy, Department of Pathology and Biobank (BB-0033-00035), Nancy, France. 7. CHU Toulouse, Larrey Hospital, Université Paul Sabatier, Toulouse, France. 8. Normandie Université, Department of Pathology, Caen, France. 9. CHU Bordeaux, Department of Pathology, Pessac, France. 10. Université Côte d'Azur, University Hospital Federation OncoAge, Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France; Université Côte d'Azur, CNRS, INSERM, Institute of Research on Cancer and Ageing of Nice (IRCAN), University Hospital Federation OncoAge, Nice, France. 11. Université Côte d'Azur, University Hospital Federation OncoAge, Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France. 12. Université Côte d'Azur, CNRS, INSERM, Institute of Research on Cancer and Ageing of Nice (IRCAN), University Hospital Federation OncoAge, Nice, France; Université Côte d'Azur, University Hospital Federation OncoAge, Department of Pulmonary Medicine and Thoracic Oncology, Nice, France. 13. Université Côte d'Azur, University Hospital Federation OncoAge, Department of Pulmonary Medicine and Thoracic Oncology, Nice, France. 14. Université Côte d'Azur, University Hospital Federation OncoAge, Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France; Université Côte d'Azur, CNRS, INSERM, Institute of Research on Cancer and Ageing of Nice (IRCAN), University Hospital Federation OncoAge, Nice, France; Université Côte d'Azur, University Hospital Federation OncoAge, Hospital-Related Biobank (BB-0033-00025), Pasteur Hospital, Nice, France. Electronic address: hofman.p@chu-nice.fr.
Abstract
INTRODUCTION: The detection of a ROS1 rearrangement in advanced and metastatic lung adenocarcinoma (LUAD) led to a targeted treatment with tyrosine kinase inhibitors with favorable progression-free survival and overall survival of the patients. Thus, it is mandatory to screen for the ROS1 rearrangement in all these patients. ROS1 rearrangements can be detected using break-apart fluorescence in situ hybridization (FISH), which is the gold standard; however, ROS1 immunohistochemistry (IHC) can be used as a screening test because it is widely available, easy and rapid to perform, and cost-effective. METHODS: We evaluated the diagnostic accuracy and interpathologist agreement of two anti-ROS1 IHC clones, SP384 (Ventana, Tucson, Arizona) and D4D6 (Cell Signaling, Danvers, Massachusetts), in a training cohort of 51 positive ROS1 FISH LUAD cases, and then in a large validation cohort of 714 consecutive cases of LUAD from six routine molecular pathology platforms. RESULTS: In the two cohorts, the SP384 and D4D6 clones show variable sensitivity and specificity rates on the basis of two cutoff points greater than or equal to 1+ (all % tumor cells) and greater than or equal to 2+ (>30% stained tumor cells). In the validation cohort, the D4D6 yielded the best accuracy for the presence of a ROS1 rearrangement by FISH. Interpathologist agreement was moderate to good (interclass correlation 0.722-0.874) for the D4D6 clone and good to excellent (interclass correlation: 0.830-0.956) for the SP384 clone. CONCLUSIONS: ROS1 IHC is an effective screening tool for the presence of ROS1 rearrangements. However, users must be acutely aware of the variable diagnostic performance of different anti-ROS1 antibodies before implementation into routine clinical practice.
INTRODUCTION: The detection of a ROS1 rearrangement in advanced and metastatic lung adenocarcinoma (LUAD) led to a targeted treatment with tyrosine kinase inhibitors with favorable progression-free survival and overall survival of the patients. Thus, it is mandatory to screen for the ROS1 rearrangement in all these patients. ROS1 rearrangements can be detected using break-apart fluorescence in situ hybridization (FISH), which is the gold standard; however, ROS1 immunohistochemistry (IHC) can be used as a screening test because it is widely available, easy and rapid to perform, and cost-effective. METHODS: We evaluated the diagnostic accuracy and interpathologist agreement of two anti-ROS1 IHC clones, SP384 (Ventana, Tucson, Arizona) and D4D6 (Cell Signaling, Danvers, Massachusetts), in a training cohort of 51 positive ROS1 FISH LUAD cases, and then in a large validation cohort of 714 consecutive cases of LUAD from six routine molecular pathology platforms. RESULTS: In the two cohorts, the SP384 and D4D6 clones show variable sensitivity and specificity rates on the basis of two cutoff points greater than or equal to 1+ (all % tumor cells) and greater than or equal to 2+ (>30% stained tumor cells). In the validation cohort, the D4D6 yielded the best accuracy for the presence of a ROS1 rearrangement by FISH. Interpathologist agreement was moderate to good (interclass correlation 0.722-0.874) for the D4D6 clone and good to excellent (interclass correlation: 0.830-0.956) for the SP384 clone. CONCLUSIONS:ROS1 IHC is an effective screening tool for the presence of ROS1 rearrangements. However, users must be acutely aware of the variable diagnostic performance of different anti-ROS1 antibodies before implementation into routine clinical practice.
Authors: Richard S P Huang; Amanda Gottberg-Williams; Panhia Vang; Shoua Yang; Nicholas Britt; Jaspreet Kaur; James Haberberger; Natalie Danziger; Clarence Owens; Sara E Beckloff; Jeffrey S Ross; Shakti H Ramkissoon Journal: JTO Clin Res Rep Date: 2020-09-18