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

• Published in: PloS one 2015-04, Vol.10 (4), p.e0124354-e0124354
• Main Authors: Fu, Sha, Liang, Ying, Lin, Yong-Bin, Wang, Fang, Huang, Ma-Yan, Zhang, Zi-Chen, Wang, Jing, Cen, Wen-Jian, Shao, Jian-Yong
• Format: Article
• Language: English
• Subjects: Aged; Cancer; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - surgery; Care and treatment; Cell survival; Cytogenetics; Female; Fluorescence; Fluorescence in situ hybridization; Gene Rearrangement; Humans; Immunohistochemistry; Lung cancer; Lung diseases; Lung Neoplasms - genetics; Lung Neoplasms - surgery; Male; Medical prognosis; Middle Aged; Multivariate analysis; Non-small cell lung cancer; Non-small cell lung carcinoma; Patients; Prognosis; Protein-Tyrosine Kinases - genetics; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-ret - genetics; Retrospective Studies; Small cell lung cancer; Squamous cell carcinoma; Surgery; Tumor cells; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0124354

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.