Primary concomitant EGFR T790M mutation predicted worse prognosis in non-small cell lung cancer patients
Authors Li H, Hu H, Wang R, Pan Y, Wang L, Li Y, Zhang Y, Ye T, zhang Y, Li B, Shen L, Sun Y, Chen H
Received 5 January 2014
Accepted for publication 1 February 2014
Published 3 April 2014 Volume 2014:7 Pages 513—524
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 4
Hang Li,1,2,* Haichuan Hu,1,2,* Rui Wang,1,2 Yunjian Pan,1,2 Lei Wang,1,2 Yuan Li,2,3 Yang Zhang,1,2 Ting Ye,1,2 Yiliang Zhang,1,2 Bin Li,1,2 Lei Shen,2,3 Yihua Sun,1,2 Haiquan Chen1,2
1Department of Thoracic Surgery, 2Department of Oncology, 3Department of Pathology, Shanghai Medical College, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
*These authors contributed equally to this work
Purpose: We performed this analysis to improve the understanding of the clinicopathological characteristics and clinical outcome of non-small cell lung cancer (NSCLC) patients harboring the primary epidermal growth factor receptor (EGFR) T790M mutation along with activating EGFR mutation.
Methods: Resected tumors from 1903 NSCLC patients were analyzed for mutation in EGFR, as well as KRAS (Kirsten rat sarcoma viral oncogene homolog), BRAF (v-raf murine sarcoma viral oncogene homolog B), HER2 (human epidermal growth factor 2), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha), and EML4 (echinoderm microtubule associated protein like 4)-ALK (anaplastic lymphoma receptor tyrosine kinase) fusion. Fluorescence in situ hybridization was performed to define EGFR and c-MET (met proto-oncogene gene amplification. Expression of PIK3CA and p-Akt (phosphorylated protein kinase B) were tested using immunohistochemistry. Clinical and pathological data, including sex, age at diagnosis, stage, tumor differentiation, smoking history, histological subtype, relapse-free and overall survival, were further analyzed.
Results: In all, 16 NSCLC patients were found to harbor primary EGFR T790M mutation, including 14 adenocarcinomas and two adenosquamous carcinomas, accounting for 2.04% of all the EGFR mutant cases and 0.84% of the total. No c-MET amplification was found to coexist with primary EGFR T790M. Fewer EGFR copy-number variations were found in samples harboring EGFR T790M mutations compared with those in patients with exon 19 deletions and L858R. Overall survival was significantly shorter for patients harboring EGFR T790M mutation than it was for patients with exon 19 deletions (logrank P=0.008). When taking patients harboring EGFR L858R or exon 19 deletions as one group, the overall survival was also significantly longer than that in patients with T790M mutation (logrank P=0.012). There was no significant difference in relapse-free survival among three subgroups of patients.
Conclusion: Our study described the clinicopathological and molecular characteristics of NSCLC patients harboring primary EGFR T790M mutations. Its value of being a predictor for worse prognosis was established. Primary EGFR T790M mutation is a rare event in NSCLC cases, but the therapeutic strategies for this subtype of patients should be precisely considered.
Keywords: driver mutation, survival, clinicopathological profile, EGFR tyrosine kinase inhibitor, acquired resistance
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