1193P - Oncogenic driver mutations in Chinese non-small cell lung cancer (NSCLC)

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Non-Small-Cell Lung Cancer, Locally Advanced
Pathology/Molecular Biology
Presenter Jianxing He
Authors J. He1, H. Yang2, Q. Deng3, P. He2, J. Jiang4, M. Zhao2, X. Gu5, L. Zheng6, H. Pang4, J.X. Zhou7
  • 1The First Affiliated Hospital of Guangzhou Medical University, 510120 - Guangzhou/CN
  • 2Thoracic Oncology, The First Affiliated Hospital of Guangzhou Medical University, 510120 - Guangzhou/CN
  • 3The Center For Translational Medicine, The First Affiliated Hospital of Guangzhou Medical University, 510120 - Guangzhou/CN
  • 4Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, 510120 - Guangzhou/CN
  • 5Pathology, The First Affiliated Hospital of Guangzhou Medical University, 510120 - Guangzhou/CN
  • 6The Center For Translational Medicine, Xiamen University, 361005 - Xiamen/CN
  • 7Ningbo University School of Medicine, 325211 - Ningbo/CN

Abstract

Background

Oncogenic driver mutations are responsible for both the initiation and maintenance of cancers including NSCLC. Elucidation of driver mutation occurrence in NSCLC and its relationship with clinical outcome are imperative to personalized treatment of NSCLC.

Methods

Tumor tissues from a total of 488 Chinese NSCLC patients at various stages were enrolled in this retrospective study. Mutations were assessed using amplification-refractory mutation system (ADx-ARMSTM)-PCR and verified using direct sequencing. ERCC1 levels were measured using immunohistochemistry method. The relationship between tumor gene mutation status and patient's disease-free survival (DFS) was analyzed.

Results

Of the 488 NSCLC tumors, 28 had EML4-ALK fusions (5.7%). Female (10.38%), young age (<60-year old) (7.9%), and non-smoking patients (8.2%) had significant greater mutation rates than male (3.1%), old age (≥60-year old) (3.6%), and smoking patients (2.6%), respectively (for all P < 0.05). In addition, EML4-ALK fusions were observed in adenocarcinoma (7.2%) more than in squamous-cell carcinoma (2.0%) (P = 0.05). In stage IA patients (n = 134), the rate of EML4-ALK fusions was 9%, and in stage IIIA patients the rate was 5.5% (n = 165). Of 392 NSCLC samples, 13 had PIK3CA mutations (3.3%) and 3 had MEK1 mutations (0.8%). EML4-ALK, PIK3CA, and MEK1 mutations were mutually exclusive. However, EML4-ALK fusion was found to be of co-existence with EGFR and KRAS mutations in two cases. In stage IA NSCLC, EML4-ALK fusion-positive patients had longer DFS than those EML4-ALK fusion-negative patients (P = 0.04). However, in stage IIIA NSCLC, EML4-ALK fusion-positive patients had poorer DFS than those EML4-ALK fusion-negative patients (P = 0.0057). Moreover, multivariate Cox proportional hazard analysis indicated that in stage IIIA NSCLC EML4-ALK fusion was the only significant predictor for poor DFS (HR = 4.4, 95% CI 2.0-9.7, P < 0.001). We further found that ERCC1 was highly expressed in EML4-ALK fusion-positive tumors.

Conclusion

Oncogenic driver mutations define molecular subsets of Chinese NSCLC patients with distinct clinicopathological characteristics. EML4-ALK fusion might be a significant prognostic biomarker for locally advanced stage NSCLC.

Disclosure

All authors have declared no conflicts of interest.