Pathology & Oncology Research

, 15:651

Clinicopathologic and Molecular Features of Epidermal Growth Factor Receptor T790M Mutation and c-MET Amplification in Tyrosine Kinase Inhibitor-resistant Chinese Non-small Cell Lung Cancer

  • Hua-Jun Chen
  • Tony S. Mok
  • Zhi-Hong Chen
  • Ai-Lin Guo
  • Xu-Chao Zhang
  • Jian Su
  • Yi-Long Wu
Original Paper

DOI: 10.1007/s12253-009-9167-8

Cite this article as:
Chen, HJ., Mok, T.S., Chen, ZH. et al. Pathol. Oncol. Res. (2009) 15: 651. doi:10.1007/s12253-009-9167-8

Abstract

To investigate the clinicopathologic and molecular features of the T790M mutation and c-MET amplification in a cohort of Chinese non-small cell lung cancer (NSCLC) patients resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). EGFR TKI-resistant NSCLC patients (n = 29) and corresponding tumor specimens, and 53 samples of postoperative TKI-naïve NSCLC patients were collected. EGFR exon 19, 20, and 21 mutations were analyzed. And c-MET gene copy number was determined. The EGFR T790M mutation in exon 20 was not detected in the population of 53 TKI-naïve patients, but found in 48.3% (14/29) of the enrolled TKI-resistant patients. c-MET was amplified in 3.8% (2/53) of the TKI-naïve NSCLC patients and highly amplified in 17.2% (5/29) of the cohort. Most of T790M mutations were frequently associated with non-smoker, adenocarcinoma and EGFR activating mutations. Three male patients with T790M mutation occurred with wild-type EGFR, and were resistant to the treatments following TKI resistance. Features of c-MET amplification in TKI-naïve patients were indistinguishable from TKI-resistant patients. In the group of wild-type EGFR, patients with T790M mutation had median progression free survival (PFS) and overall survival (OS) as 9.6 months and 12.6 months, respectively; whereas the median PFS and OS of c-MET amplified patients was 4.1 months and 8.0 months, respectively. These results suggest that EGFR T790M mutation and c-MET amplification can occur in TKI-resistant NSCLC with wild-type EGFR, and these genetic defects might be related to different survival outcome. c-MET amplification in TKI-naïve or -resistant patients might share similarities in clinicopathologic features.

Keywords

c-MET Epidermal growth factor receptor Non-small cell lung cancer, Resistance T790M 

Abbreviations

(ARMS)

amplification refractory mutation system

(EGFR)

epidermal growth factor receptor

(NSCLC)

non-small cell lung cancer

(OS)

overall survival

(PFS)

progression free survival

(TKI)

tyrosine kinase inhibitor

Copyright information

© Arányi Lajos Foundation 2009

Authors and Affiliations

  • Hua-Jun Chen
    • 1
    • 2
  • Tony S. Mok
    • 3
  • Zhi-Hong Chen
    • 2
  • Ai-Lin Guo
    • 4
  • Xu-Chao Zhang
    • 4
  • Jian Su
    • 2
  • Yi-Long Wu
    • 2
  1. 1.Cancer CenterSun Yat-Sen UniversityGuangzhouChina
  2. 2.Guangdong Lung Cancer InstituteGuangdong General HospitalGuangzhouChina
  3. 3.Department of Clinical OncologyChinese University of Hong KongHong KongChina
  4. 4.Department of BiochipGuangdong Academy of Medical SciencesGuangzhouChina

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