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

Sha Fu,Ma-Yan Huang,Ying Liang,Yong-Bin Lin,Jing Wang,Wen-Jian Cen,Zi-Chen Zhang,Fang Wang,Jian-Yong Shao,Domenico Coppola

doi:10.1371/journal.pone.0124354

Sha Fu, Ma-Yan Huang + Show 8 more

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https://doi.org/10.1371/journal.pone.0124354

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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.

Highlights

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers [1]
The aim of this study was to determine the frequency of ros oncogene 1 (ROS1) and ret proto-oncogene (RET) rearrangements and their relationship with clinicopathological characteristics in resected stage IIIA-N2 NSCLC and to provide guidance for future clinical treatment
ROS1 and RET rearrangements appear to occur in approximately 2% of NSCLC [22,23,24,38,39]

Summary

Introduction

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers [1]. Complete resection is the most effective treatment for patients with lung cancer, but postoperative survival remains unsatisfactory, especially for the IIIA NSCLC [2,3]. IIIA NSCLC is defined as locally advanced NSCLC, and the resection rate of which is only 14–20% [4]. These patients are offered different postoperative adjuvant treatments according to different N stages. The 5-year survival rate after surgery for IIIA-N2 NSCLC patients is approximately 20%, and 30% patients have recurrences and metastases within five years [4,6]. Significant discrepant clinical outcomes in IIIA-N2 NSCLC patients require a novel and effective therapy

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