The Frequency and Clinical Implication of ROS1 and RET Rearrangements in Resected Stage IIIA-N2 Non-Small Cell Lung Cancer Patients

Abstract

To evaluate the frequency and clinicopathological features of ROS1 and RET rearrangements in N2 node positive stage IIIA (IIIA-N2) non-small cell lung cancer (NSCLC) patients, we retrospectively screened 204 cases with a tissue microarray (TMA) panel by fluorescent in situ hybridization (FISH), and confirmed by direct sequencing and immunohistochemistry (IHC). The relationship between ROS1 or RET rearrangements, clinicopathological features, and prognostic factors were analyzed in resected stage IIIA-N2 NSCLC. Of the 204 cases, 4 cases were confirmed with ROS1 rearrangement, but no RET rearrangement was detected. All 4 ROS1-rearranged cases were adenocarcinomas. The predominant pathological type was acinar pattern in ROS1-rearranged tumors, except for 1 case harboring a mixture acinar and mucous tumor cells. Variants of ROS1 rearrangement were SDC4-ROS1 (E2:E32), SDC4-ROS1 (E4:E32) and SDC4-ROS1 (E4:E34). There was no significant association between ROS1 rearrangement and clinicopathological characteristics. In this cohort, multivariate analysis for overall survival (OS) indicated that squamous cell carcinoma and lobectomy were independent predictors of poor prognosis; R0 surgical resection and non-pleural invasion were independent predictors of good prognosis. In resected stage IIIA-N2 NSCLC patients, ROS1-rearranged cases tended to occur in younger patients with adenocarcinomas. The prognosis of resected stage IIIA-N2 is generally considered poor, but patients with ROS1 rearrangement will benefit from the targeted therapy.

A Validation Study for the Use of ROS1 Immunohistochemical Staining in Screening for ROS1 Translocations in Lung Cancer

“…Sensitivity and specificity using an h-score of 100 were 100% and 83%, respectively, which is in keeping with most of the published literature (Table 3). 12,14,15,[17][18][19][20][21][22] This study also highlights the importance of individual laboratory validation of a screening program, given the variation in platforms, antibody dilutions, and optimization techniques reflecting the real-life variation in laboratory facilities. Even our chosen thickness of slides for FISH varied from that of other studies (2 mm versus 3-4 mm), this having been internally validated as not affecting FISH results but saving tissue.…”

Clinicopathological significance and diagnostic approach of ROS1 rearrangement in non-small cell lung cancer: a meta-analysis: ROS1 in non-small cell lung cancer

“…Data from all eligible studies were extracted by two independent authors. The included data were extracted from each of the eligible studies: 2,13–32 the first author’s name, the year of publication, the study location, the detection method for ROS1 genetic alteration, and the number of patients analyzed. For the meta-analysis, we extracted all data associated with the results of ROS1 genetic alteration and IHC.…”

Lung cancer family history and exposure to occupational/domestic coal combustion contribute to variations in clinicopathologic features and gene fusion patterns in non‐small cell lung cancer

“…62 Our results regarding ALK and ROS1 fusion were similar to previous reports with the exception of elevated ROS1 fusion frequency (3.9%). 29,30,49,62 A meta-analysis including 1178 ALK rearranged cases from 20 541 NSCLC patients indicated that age, gender, smoking status, histology, tumor stage, and ethnicity may be a source of between-study heterogeneity. 19 According to the reference studies from three nations, there is obvious across population/subpopulation similarity and heterogeneity.…”

“…The primers and PCR conditions were designed based on previous studies (Table S1). The PCR conditions were as follows: 95°C, 5 minutes, 10 cycles of touchdown PCR (annealing from 63 to 58°C with a 0.5 decrease each cycle) and 30 cycles of 95°C, 40 seconds, 58°C, 40 seconds, 72°C, 1 minute, with a final extension of 72°C for 5 minutes.…”