Frequent aerogenous spread with decreased E-cadherin expression of ROS1-rearranged lung cancer predicts poor disease-free survival.

Abstract

ROS1 rearrangement has been found in a subset of lung cancer and ROS1-rearranged tumors are sensitive to ALK kinase inhibitors. This study sought to evaluate the clinicopathological implications and histomorphological characteristics of ROS1-rearranged tumors, especially micropapillary and aerogenous spread growth and to investigate the usefulness of ROS1 immunohistochemistry as a diagnostic test for ROS1 rearrangement. ROS1 rearrangement characterizations by fluorescence in situ hybridization and ROS1 protein and E-cadherin expression by immunohistochemistry were performed using 754 non-small cell lung cancer surgical specimens. ROS1 rearrangement was identified in 10 samples. Histologically, all 10 ROS1-rearranged tumors harbored an adenocarcinoma component. Significantly, we noted a high association between ROS1 rearrangement with a micropapillary component (p<0.001), aerogenous spread (p=0.002), and E-cadherin loss (p=0.049). Survival analysis showed that ROS1 rearrangement was significantly associated with a higher risk of tumor recurrence (p=0.024). The best criterion to detect ROS1-rearrangement by immunohistochemistry was an H-score of ≥100, with a sensitivity and specificity of 90% and 93.5%, respectively. ROS1-rearranged adenocarcinoma exhibited distinct morphological and clinicopathological features. Decreased membranous E-cadherin expression and aerogenous spread may be associated with worse disease-free survival. ROS1 immunohistochemistry correlated well with ROS1 gene rearrangement.