Oral Presentation COSA-IPOS Joint Scientific Meeting 2012

Patterns of DNA mutations in resected early stage node negative lung adenocarcinoma. (#28)

Po Yee Yip 1 2 3 , Bing Yu 3 4 , Wendy A Cooper 5 6 , Chu Chin Ng 4 , Christina I Selinger 5 , Maija M Kohonen-Corish 2 6 7 , Brian C McCaughan 8 , Catherine Kennedy 8 , Ronald J Trent 3 4 , Michael J Boyer 1 3 , James G Kench 2 3 5 , Sandra A O'Toole 2 3 4 5 , Lisa G Horvath 1 2 3
  1. Sydney Cancer Centre, Camperdown, NSW, Australia
  2. Cancer Program, Kinghorn Cancer Centre and Garvan Institute of Medical Research, Sydney, Australia
  3. Sydney Medical School, University of Sydney, Sydney, Australia
  4. Molecular and Clinical Genetics, Royal Prince Alfred Hospital, Sydney, Australia
  5. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia
  6. School of Medicine, University of Western Sydney, Sydney, Australia
  7. St Vincent's Clinical School, University of Western Sydney, Sydney, Australia
  8. Cardiothoracic Surgery, Royal Prince Alfred Hospital, Sydney, Australia

Background: Many studies have examined specific mutations in patients with resected lung adenocarcinoma across a heterogeneous group of stages predominantly advanced stage, but there is relatively little data regarding the mutation profile of patients with early stage node negative disease. The aim of this study is to identify patterns of mutations in early stage node negative lung adenocarcinoma.

Methods: Two hundred and four patients who underwent resection for stage IB (6th Ed AJCC) lung adenocarcinoma and received no adjuvant treatment were identified. Their tumours were genotyped using the OncoCarta v1.0 kit and processed on the Sequenom compact Mass ARRAY platform. FISH for ALK rearrangement was also performed.

Results: There were 117 (57.4%) patients whose tumours harbored at least one mutation. KRAS, EGFR, PIK3CA, MET, ALK rearrangement and less common mutations (PDGFRA, AKT1, BRAF, FGFR1 and HRAS) were detected in tumours from 77 (37.7%), 29 (14.2%), 9 (4.4%), 7 (3.4%), 2 (1%) and 6 (3%) patients respectively. Synchronous mutations (either co-mutations or double mutations) were identified in 18 (8.8%) patients. KRAS and PIK3CA mutations were associated with poorly differentiated tumours (p=0.032; p=0.018) while EGFR mutations were associated with well-differentiated tumours (p=0.001). There was one tumour harbored an EGFR T790M mutation and four tumours had EGFR exon 20 insertions mutations, all of which are known to associate with resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs).

Conclusions: There are diverse patterns of mutations in resected early stage node-negative lung adenocarcinoma including EGFR mutations which are associated with resistance to EGFR-TKIs therapy. These data may influence the design of future adjuvant targeted therapy trials.