High prevalence of ROS1 gene rearrangement detected by FISH in EGFR and ALK negative lung adenocarcinoma

Abstract

ROS1 rearrangement has become an important biomarker for targeted therapy in advanced lung adenocarcinoma (LUAD). The study aimed to evaluate the prevalence of ROS1 rearrangement in Chinese LUAD with EGFR wild-type and ALK fusion-negative status, and analyze the relationship with their clinicopathological characteristics. A large cohort of 589 patients of LUAD with EGFR/ALK wild-type, diagnosed between April 2014 and June 2018, was retrospectively analyzed. ROS1 rearrangement in all these cases was detected by FISH, and 8 selected cases with different positive and negative signals were confirmed by NGS. As a result, total of 56 cases with ROS1 rearrangements out of 589 LUADs (9.51%) were identified by FISH. The frequency of ROS1 rearrangement in women was 22.15% (35/158), which was statistically higher than 4.87% (21/431) in men (P < 0.001). The ROS1 positive rate in the patients with age < 50 years old (25.29%, 22/87) was statistically higher than that in the patients with age ≥ 50 (6.77%, 34/502) (P < 0.001). There was a trend that the frequency of ROS1 rearrangement in LUAD with stage III-IV was higher than that in stage I-II (9.56%, 39/408 vs 2.50%, 1/40), although it did not reach significant difference (P = 0.135). 37 out of 56 cases of ROS1 rearranged LUAD showed solid (n = 20, 35.71%) and invasive mucinous adenocarcinoma (n = 17, 30.36%) pathological subtypes. The median OS for patients of ROS1 rearranged LUAD treated with TKIs (n = 29) was 49.69 months (95% CI: 36.71, 62.67), compared with 32.55 months (95% CI: 23.24, 41.86) for those who did not receive TKI treatment (n = 16) (P = 0.040). The NGS results on ROS1 rearrangement in all the 8 cases were concordant with FISH results. In conclusion, high prevalence of ROS1 rearrangements occurs in EGFR/ALK wild-type LUAD detected by FISH, especially in younger, female, late stage patients, and in histological subtypes of solid and invasive mucinous adenocarcinoma.