- Volume 17 Issue 3
Aims: To investigate the distribution of epidermal growth factor receptor (EGFR) mutations, and explore any relationships with clinical characteristics in non-small-cell lung carcinoma (NSCLC) patients. Materials and Methods: EGFR mutations were assessed by ADx-ARMS in 261 NSCLC patients from West China Hospital of Sichuan University. Relationships between EGFR mutation and clinical characteristics were analyzed by SPSS. Results: The EGFR mutation rate was 48.7% (127/261), 19-del and L858R mutations occurred predominantly, accounting for 33.1% and 40.9%, respectively, in mutated cases. Moreover, 10.2% patients were found to carry double mutations. EGFR mutations occurred more frequently in women (57.5%) than in men (41.8%) (P=0.01), and were more frequent in non-smokers (61.2%) than in former or current smokers (31.2%) (P<0.00). In addition, they were more common in adenocarcinomas (52.8%) and adenosquamous carcinomas (42.8%) than in squamous cell carcinomas (14.8%) (p<0.00). However, only smoking history and pathological types, rather than gender, proved to be associated with EGFR mutations on multivariate logistic regression analysis. No significant differences in pathological stage and metastasis status were found between EGFR wild-type and mutated cases, although EGFR mutation type was related to pathological type (p=0.00) - 19-del, L858R and other mutation types respectively occurred in 34.2%, 42.5% and 23.3% of adenocarcinomas, but in 14.3%, 0% and 85.7% of non-adenocarcinomas. Conclusions: The EGFR mutation rate was 48.7% in NSCLCs in Southwest China, so that nearly 40% patients might benefit from targeted therapies. Smoking status and pathological types were independent predictors of EGFR mutation, while EGFR mutation type was related to only pathological type, rather than smoking status.
Non-small-cell lung carcinoma;mutation;epidermal growth factor receptor;Southwest China
- Dong DD, Tang Y, Zou Y, et al (2011). Study of exons 19 and 21 mutations of epidermal growth factor receptor gene in patients with lung adenocarcinoma of Sichuan Province. Chinese J Clin Experimental Pathol, 27, 1306-9.
- Dong QG, Han BH, Huang JS, et al (2006). Analysis of EGFR mutations in 176 cases of non-small cell lung cancer. Chinese J Oncol, 28, 686-90.
- Doss GP, Rajith B, Chakraborty C, et al (2014). Structural signature of the G719S-T790M double mutation in the EGFR kinase domain and its response to inhibitors. Sci Rep, 4, 5868.
- Eck MJ, Yun CH (2010). Structural and mechanistic underpinnings of the differential drug sensitivity of EGFR mutations in non-small cell lung cancer. Biochim Biophys Acta, 1804, 559-66. https://doi.org/10.1016/j.bbapap.2009.12.010
- Gahr S, Stoehr R, Geissinger E, et al (2013). EGFR mutational status in a large series of Caucasian European NSCLC patients: data from daily practice. Br J Cancer, 109, 1821-8. https://doi.org/10.1038/bjc.2013.511
- Gu D, Scaringe WA, Li K, et al (2007). Database of somatic mutations in EGFR with analyses revealing indel hotspots but no smoking-associated signature. Hum Mutat, 28, 760-70. https://doi.org/10.1002/humu.20512
- Kobayashi S, Boggon TJ, Dayaram T, et al (2005). EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med, 352, 786-92. https://doi.org/10.1056/NEJMoa044238
- Koo DH, Kim KP, Choi CM, et al (2015). EGFR-TKI is effective regardless of treatment timing in pulmonary adenocarcinoma with EGFR mutation. Cancer Chemother Pharmacol, 75, 197-206. https://doi.org/10.1007/s00280-014-2631-5
- Liam CK, Leow HR, How SH, et al (2014). Epidermal growth factor receptor mutations in non- small cell lung cancers in a multiethnic malaysian patient population. Asian Pac J Cancer Prev, 15, 321-6. https://doi.org/10.7314/APJCP.2014.15.1.321
- Lin LA, Liu ZY, Yang JS, et al (2014). Distribution and clinical significance of EGFR mutations in phase I non-small-cell lung cancer. Chinese J Thoracic Cardiovascular Surgery, 30.
- Lowder MA, Doerner AE, Schepartz A (2015). Structural Differences between Wild-Type and Double Mutant EGFR Modulated by Third-Generation Kinase Inhibitors. J Am Chem Soc, 137, 6456-9. https://doi.org/10.1021/jacs.5b02326
- Lynch TJ, Bell DW, Sordella R, et al (2004). Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med, 350, 2129-39. https://doi.org/10.1056/NEJMoa040938
- Mansuet-Lupo A, Bobbio A, Blons H, et al (2014). The new histologic classification of lung primary adenocarcinoma subtypes is a reliable prognostic marker and identifies tumors with different mutation status: the experience of a French cohort. Chest, 146, 633-43. https://doi.org/10.1378/chest.13-2499
- Matam K, Goud I, Lakshmi MA, et al (2015). Correlation between EGFR Gene Mutations and Lung Cancer: a Hospital-Based Study. Asian Pac J Cancer Prev, 16, 7071-6. https://doi.org/10.7314/APJCP.2015.16.16.7071
- Mitsudomi T, Kosaka T, Endoh H, et al (2005). Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence. J Clin Oncol, 23, 2513-20. https://doi.org/10.1200/JCO.2005.00.992
- Mok TS, Wu YL, Thongprasert S, et al (2009). Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med, 361, 947-57. https://doi.org/10.1056/NEJMoa0810699
- Naderi S, Ghorra C, Haddad F, et al (2015). EGFR mutation status in Middle Eastern patients with non-squamous non-small cell lung carcinoma: A single institution experience. Cancer Epidemiol, 39, 1099-102. https://doi.org/10.1016/j.canep.2015.08.016
- National Office for Cancer Prevention and Control NCfCR, Disease Prevention and Control Bureau, Ministry of HealthNational Office for Cancer Prevention and Control, National Center for Cancer Registry, Disease Prevention and Control Bureau, Ministry of Health (2010). Chinese cancer mortality report: Third national retrospect spot-check of death-causation. Beijing, China: People's Medical Publishing House, 35.
- Pao W, Hutchinson KE (2012). Chipping away at the lung cancer genome. Nat Med, 18, 349-51. https://doi.org/10.1038/nm.2697
- Rosell R, Moran T, Queralt C, et al (2009). Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med, 361, 958-67. https://doi.org/10.1056/NEJMoa0904554
- Sahoo R, Harini VV, Babu VC, et al (2011). Screening for EGFR mutations in lung cancer, a report from India. Lung Cancer, 73, 316-9. https://doi.org/10.1016/j.lungcan.2011.01.004
- Shaozhang Z, Ming Z, Haiyan P, et al (2014). Comparison of ARMS and direct sequencing for detection of EGFR mutation and prediction of EGFR-TKI efficacy between surgery and biopsy tumor tissues in NSCLC patients. Med Oncol, 31, 926. https://doi.org/10.1007/s12032-014-0926-3
- She J, Yang P, Hong Q, et al (2013). Lung cancer in China: challenges and interventions. Chest, 143, 1117-26. https://doi.org/10.1378/chest.11-2948
- Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al (2005). Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med, 353, 123-32. https://doi.org/10.1056/NEJMoa050753
- Shi Y, Au JS, Thongprasert S, et al (2014). A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol, 9, 154-62. https://doi.org/10.1097/JTO.0000000000000033
- Sholl LM, Aisner DL, Varella-Garcia M, et al (2015). Multiinstitutional Oncogenic Driver Mutation Analysis in Lung Adenocarcinoma: The Lung Cancer Mutation Consortium Experience. J Thorac Oncol, 10, 768-77. https://doi.org/10.1097/JTO.0000000000000516
- Tang Y, Zhang L, Tan X, et al (2014). Analysis of EGFR mutations in non-small cell lung cancer in Nanning Guangxi China. J Modern Oncol.
- Tian H, Kaizhong YU, Mao Z, et al (2014). Study on mutation of EGFR gene in 314 cases of non-small cell lung cancers. J Shanxi Medical University.
- Tomita M, Ayabe T, Chosa E, et al (2014). Epidermal growth factor receptor mutations in Japanese men with lung adenocarcinomas. Asian Pac J Cancer Prev, 15, 10627-30.
- Torre LA, Bray F, Siegel RL, et al (2015). Global cancer statistics, 2012. CA Cancer J Clin, 65, 87-108. https://doi.org/10.3322/caac.21262
- Wu YL, Zhong WZ, Li LY, et al (2007). Epidermal growth factor receptor mutations and their correlation with gefitinib therapy in patients with non-small cell lung cancer: a meta-analysis based on updated individual patient data from six medical centers in mainland China. J Thorac Oncol, 2, 430-9. https://doi.org/10.1097/01.JTO.0000268677.87496.4c
- Xue C, Hu Z, Jiang W, et al (2012). National survey of the medical treatment status for non-small cell lung cancer (NSCLC) in China. Lung Cancer, 77, 371-5. https://doi.org/10.1016/j.lungcan.2012.04.014
- Yasuda H, Kobayashi S, Costa DB (2012). EGFR exon 20 insertion mutations in non-small-cell lung cancer: preclinical data and clinical implications. Lancet Oncol, 13, 23-31. https://doi.org/10.1016/S1470-2045(11)70426-0
- Yokoyama T, Kondo M, Goto Y, et al (2006). EGFR point mutation in non-small cell lung cancer is occasionally accompanied by a second mutation or amplification. Cancer Sci, 97, 753-9. https://doi.org/10.1111/j.1349-7006.2006.00233.x
- Yoshizawa A, Sumiyoshi S, Sonobe M, et al (2013). Validation of the IASLC/ATS/ERS lung adenocarcinoma classification for prognosis and association with EGFR and KRAS gene mutations: analysis of 440 Japanese patients. J Thorac Oncol, 8, 52-61. https://doi.org/10.1097/JTO.0b013e3182769aa8
- Zhang G (2007). Molecular epidemiologic investigation of EGFR double mutations in Chinese non-small-cell lung cancer population and related studies on biological properyies. Doctoral Dissertation, 2007, 3.
- Zhang Y, Wang Q, Han ZG, et al (2013). Differences in epidermal growth factor receptor gene mutations and relationship with clinicopathological features in NSCLC between Uygur and Han ethnic groups. Asian Pac J Cancer Prev, 14, 2879-83. https://doi.org/10.7314/APJCP.2013.14.5.2879
- Zhao J, Tian Q, Huang Y, et al (2014). An Analysis of the EGFR gene mutation in 238 patients with non-small cell lung cancer in hunan province. Anti-tumor Pharmacy.
- Zheng J, Xie G, Jiao LI, et al (2014). Clinical significance of EGFR mutations in non-small cell lung cancer. Chinese J Clin Oncol, 41, 904-7.
- Zhou W, Christiani DC (2011). East meets West: ethnic differences in epidemiology and clinical behaviors of lung cancer between East Asians and Caucasians. Chin J Cancer, 30, 287-92. https://doi.org/10.5732/cjc.011.10106
- Mutation Analysis With Circulating Tumor DNA vol.141, pp.7, 2017, https://doi.org/10.5858/arpa.2016-0083-OA
- miR-138 suppresses the proliferation, metastasis and autophagy of non-small cell lung cancer by targeting Sirt1 vol.37, pp.6, 2017, https://doi.org/10.3892/or.2017.5619
- FGFR genes mutation is an independent prognostic factor and associated with lymph node metastasis in squamous non-small cell lung cancer pp.1555-8576, 2018, https://doi.org/10.1080/15384047.2018.1480294
- Different subtypes of EGFR exon19 mutation can affect prognosis of patients with non-small cell lung adenocarcinoma vol.13, pp.11, 2018, https://doi.org/10.1371/journal.pone.0201682
Supported by : National Natural Science Foundation of China