20. ROS1 immunohistochemistry is not a worthwhile screening test in breast carcinoma

Abstract

The FIG-ROS1 translocation was initially reported in a glioblastoma cell line, but has gained prominence in lung cancer where it has been reported in up to 2% of adenocarcinomas. ROS1 is a member of the tyrosine-kinase gene family and the FIG-ROS1 translocation results in a constitutively active tyrosine kinase which drives neoplasia. Crizotinib is a tyrosine kinase inhibitor which inactivates the ROS1 tyrosine kinase through crystallization, and has shown early promise in the treatment of lung carcinomas which harbor the FIG-ROS1 translocation. Recently a study using next generation sequencing technologies and openly available exome and transcriptome datasets suggested that up to 0.2% of breast carcinomas harbor the FIG-ROS1 translocation. It was further suggested that ROS1 expression may correlate with other features associated with poor outcome such as a high proliferative index. Immunohistochemistry has been found to be an effective screening method for ROS1 translocations in lung cancer, however few studies have been done to evaluate its applicability to breast cancer. We sought to investigate the role of screening immunohistochemistry for ROS1 as a potential marker of targeted therapy in a large cohort of breast carcinoma. We constructed a tissue microarray (TMA) including all patients with breast cancer identified from the database of the department of Anatomical Pathology Royal North Shore Hospital from 2009 to 2012. Screening immunohistochemistry for ROS1 (clone D4D6) was performed on the TMAs and for any cases with any potential staining, immunohistochemistry was repeated on whole sections. None of 631 patients (mean age 61, 99% female) consecutive breast carcinomas demonstrated any positive staining. We conclude that immunohistochemistry for ROS1 is not a worthwhile screening test in breast cancer.