RESUMEN
Introduction: The development of several ROS1 inhibitors means that the importance of accurately identifying ROS1-positive lung cancer patients has never been greater. Therefore, it is crucial that ROS1 testing assays become more standardized.Areas covered: Based on primary literature, combined with personal diagnostic and research experience, this review provide a pragmatic update on the use of the recently released VENTANA ROS1 (SP384) Rabbit Monoclonal Primary Antibody.Expert opinion: This assay provides high sensitivity, so it is an excellent analytical option when screening for ROS1 fusions in patients with advanced non-small cell lung carcinomas.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Anticuerpos Monoclonales , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteínas Tirosina Quinasas , Proteínas Proto-OncogénicasRESUMEN
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.