- Volume 14 Issue 6
DOI QR Code
Relationship between Epidermal Growth Factor Receptor Gene Mutations and Clinicopathological Features in Patients with Non-Small Cell Lung Cancer in Western Turkey
- Unal, Olcun Umit (Department of Medical Oncology, Dokuz Eylul University) ;
- Oztop, Ilhan (Department of Medical Oncology, Dokuz Eylul University) ;
- Calibasi, Gizem (Institute of Oncology, Dokuz Eylul University) ;
- Baskin, Yasemin (Institute of Oncology, Dokuz Eylul University) ;
- Koca, Dogan (Department of Medical Oncology, Van Training and Research Hospital) ;
- Demir, Necla (Department of Medical Oncology, Dokuz Eylul University) ;
- Akman, Tulay (Department of Medical Oncology, Dokuz Eylul University) ;
- Ellidokuz, Hulya (Institute of Oncology, Dokuz Eylul University) ;
- Yilmaz, Ahmet Ugur (Department of Medical Oncology, Izmir University Medical Faculty)
- Published : 2013.06.30
Background: To investigate epidermal growth factor receptor (EGFR) gene mutations in patients with non-small cell lung cancer (NSCLC) and to analyze any relationship with clinicopathological features and prognosis. Materials and Methods: EGFR gene exons 18-21 in 48 specimens of paraffin-embedded tumor tissue from NSCLC patients were amplified by PCR, followed by direct sequencing and analysis of links to clinicopathological features and prognosis. Results: EGFR mutations were detected in 18 of 48 (42.6%) patients with NSCLC. There were 9 cases of mutations in exon 20, 7 in exon 19 and 2 in exon 21. Mutations were more frequently observed in women (5/7 pts, 71.4%) than in men (13/41 pts, 31.7%) (p=0.086) and in non-smokers (5/5 pts, 100%) than smokers (13/43 pts, 30.2%). There was negative correlation of EGFR mutations with smoking status (p=0.005). EGFR mutations were more frequently observed with adenocarcinoma histology (13/32 pts, 40.6%) than in other types (5/16 pts, 31.3%) (p=0.527). The patients with EGFR mutations had better survival than those with wild-type EGFR (p=0.08). There was no association of EGFR mutations with metastatic spread. Conclusions: EGFR mutations in NSCLC were here demonstrated more frequently in females, non-smokers and adenocarcinoma histology in the western region of Turkey. Patients with EGFR mutations have a better prognosis.
EGFR mutations;non small cell lung cancer;clinical features;Western Turkey
- An SJ, Chen ZH, Su J, et al (2012). Identification of enriched driver gene alterations in subgroups of non-small cell lung cancer patients based on histology and smoking status. PLoS One, 7, 40109. https://doi.org/10.1371/journal.pone.0040109
- Arrieta O, Cardona AF, Federico BG, et al (2011). Genotyping non-small cell lung cancer (NSCLC) in Latin America. J Thorac Oncol, 6, 1955-9. https://doi.org/10.1097/JTO.0b013e31822f655f
- Cote ML, Haddad R, Edwards DJ, et al (2011). Frequency and type of epidermal growht factor mutations in African Americans with non-small cell lung cancer. J Thorac Oncol, 6, 627-30. https://doi.org/10.1097/JTO.0b013e31820a0ec0
- Davidoff AJ, Tang M, Seal B, Edelman MJ (2010). Chemotherapy and survival benefit in elderly patients with advanced non- small-cell lung cancer. J Clin Oncol, 28, 2191-7. https://doi.org/10.1200/JCO.2009.25.4052
- De Pas TM, Giovannini M, Manzotti M, et al (2011). Large-cell neuroendocrine carcinoma of the lung harboring EGFR mutation and responding to gefitinib. J Clin Oncol, 29, 819-22. https://doi.org/10.1200/JCO.2011.36.2251
- Doebele RC, Lu X, Sumey C, et al (2012). Oncogene status predicts patterns of metastatic spread in treatment-naive nonsmall cell lung cancer. Cancer, 118, 4502-11. https://doi.org/10.1002/cncr.27409
- Howlader N, Noone AM, Krapcho M, et al (2012). SEER cancer statistics review, 1975-2009. (Vintage 2009 populations). National Cancer Institute. Bethesda MD, http://seer.cancer.gov/csr/1975_2009_pops09/, based on November 2011.
- Huang YS, Yang JJ, Zhang XC, et al (2011). Impact of smoking status and pathologic type epidermal growth factor receptor mutations in lung cancer. Chin Med J, 124, 2457-60.
- Jackman DM, Yeap BY, Sequist LV, et al (2006). Exon 19 deletion mutations of epidermal growth factor receptor are associated with prolonged survival in non-small cell lung cancer patients treated with gefitinib or erlotinib. Clin Cancer Res, 12, 3908-14. https://doi.org/10.1158/1078-0432.CCR-06-0462
- Jang TW, Oak CH, Chang CK, et al (2009). EGFR and KRAS mutations in patients with adenocarcinoma of the lung. Korean J Intern Med, 24, 48-54. https://doi.org/10.3904/kjim
- Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
- Jia XL, Chen G (2011). EGFR and KRAS mutations in Chinese patients with adenosquamous carcinoma of the lung. Lung Cancer, 74, 396-400. https://doi.org/10.1016/j.lungcan.2011.04.005
- Jiang X, Liu Y, Chen C, et al (2012). The value of biomarkers in patients with sarcomatoid carcinoma of the lung: molecular analysis of 33 cases. Clin Lung Cancer, 13, 288-96. https://doi.org/10.1016/j.cllc.2011.11.004
- Laack E, Simon R, Regier M, et al (2011). Miliary neversmoking adenocarcinoma of the lung: strong association with epidermal growth factor receptor exon 19 deletion. J Thorac Oncol, 6, 199-202. https://doi.org/10.1097/JTO.0b013e3181fb7cf1
- Leary AF, Castro DG, Nicholson AG, et al (2012). Establishing an EGFR mutation screening service for nonsmall cell lung cancer-sample quality criteria and candidate histological predictors. Eur J Cancer, 48, 61-7.
- Lee S, Kim Y, Sun JM, et al (2011). Molecular profiles of EGFR, K-ras, c-met, and FGFR in pulmonary pleomorphic carcinoma, a rare lung malignancy. J Cancer Res Clin Oncol, 137, 1203-11. https://doi.org/10.1007/s00432-011-0986-0
- Lee YJ, Cho BC, Jee SH, et al (2010). Impact of environmental tobacco smoke on the incidence of mutations in epidermal growth factor receptor gene in never-smoker patients with non-small-cell lung cancer. J Clin Oncol, 28, 487-92. https://doi.org/10.1200/JCO.2009.24.5480
- Lee YJ, Shim HS, Kang YA, et al (2010). Dose effect of cigarette smoking on frequency and spectrum of epidermal growth factor receptor gene mutations in Korean patients with non-small cell lung cancer. J Cancer Res Clin Oncol, 136, 1937-44. https://doi.org/10.1007/s00432-010-0853-4
- Li M, Zhang Q, Liu L, et al (2011). The different clinical significance of EGFR mutations in exon 19 and 21 in nonsmall cell lung cancer patients of China. Neoplasma, 58, 74-81. https://doi.org/10.4149/neo_2011_01_74
- Na II, Park JH, Choe Du H, et al (2011). Association of epidermal growth factor receptor mutations with metastatic presentations in non-small cell lung cancer. ISRN Oncol, 2011, 756265.
- Nomura M, Shigematsu H, Li L, et al (2007). Polymorphisms, mutations, and amplification of the EGFR gene in non-small cell lung cancers. PLoS Med, 4, 125. https://doi.org/10.1371/journal.pmed.0040125
- NSCLC Meta-Analyses Collaborative Group(2008). Chemotherapy in addition to supportive care improves survival in advanced non-small-cell lung cancer: a systematic review and meta-analysis of individual patient data from 16 randomized controlled trials. J Clin Oncol, 26, 4617-25. https://doi.org/10.1200/JCO.2008.17.7162
- Pao W, Miller V, Zakowski M, et al (2004). EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA, 101, 13306-11. https://doi.org/10.1073/pnas.0405220101
- Qi WX, Shen Z, Lin F, et al (2012). Comparison of the efficacy and safety of EFGR tyrosine kinase inhibitor monotherapy with standard second-line chemotherapy in previously treated advanced non-small-cell lung cancer: a systematic review and meta-analysis. Asian Pac J Cancer Prev, 13, 5177-82. https://doi.org/10.7314/APJCP.2012.13.10.5177
- Ren JH, He WS, Yan GL, et al (2012). EGFR mutations in nonsmall-cell lung cancer among smokers and non-smokers: a meta-analysis. Environ Mol Mutagen, 53, 78-82. https://doi.org/10.1002/em.20680
- Saito H, Murakami S, Kondo T, et al (2012). Effectiveness of erlotinib in advanced non-small cell lung cancer in cases of gefitinib resistance after treatment of more than 6 months. Onkologie, 35, 18-22.
- Sun JM, Won YW, Kim ST, et al (2011). The different efficacy of gefitinib or erlotinib according to epidermal growth factor receptor exon 19 and exon 21 mutations in Korean nonsmall cell lung cancer patients. J Cancer Res Clin Oncol, 137, 687-94. https://doi.org/10.1007/s00432-010-0928-2
- Togashi Y, Masago K, Kubo T, et al (2011). Association of diffuse, random pulmonary metastases, including miliary metastases, with epidermal growth factor receptor mutations in lung adenocarcinoma. Cancer, 117, 819-25. https://doi.org/10.1002/cncr.25618
- Tokumo M, Toyooka S, Kiura K, et al (2005). The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers. Clin Cancer Res, 11, 1167-73.
- Toyooka S, Matsuo K, Shigematsu H, et al (2007). The impact of sex and smoking status on the mutational epidermal growth factor receptor genes in Non-small cell lung cancer. Clin Can Res, 13, 5763-8. https://doi.org/10.1158/1078-0432.CCR-07-0216
- Wu C, Hsu H, Liu H, et al (2008). Reversed mutation rates of K Ras and EGFR Genes in adenocarcinomas of the lung in Taiwan and their implications. Cancer, 113, 3199-208. https://doi.org/10.1002/cncr.23925
- Wu JY, Wu SG, Yang CH, et al (2008). Lung cancer with epidermal growth factor receptor exon 20 mutations is associated with poor gefitinib treatment response. Clin Cancer Res, 14, 4877-82. https://doi.org/10.1158/1078-0432.CCR-07-5123
- Lack of any Prognostic Role of Insulin-Like Growth Factor-1 Receptor in Non-Small Cell Lung Cancer vol.15, pp.14, 2014, https://doi.org/10.7314/APJCP.2014.15.14.5753
- Epidermal growth factor receptor and KRAS mutations in lung adenocarcinoma: A retrospective study of the Lebanese population vol.32, pp.5, 2014, https://doi.org/10.3892/or.2014.3406
- Spectrum of EGFR gene mutations and ALK rearrangements in lung cancer patients in Turkey vol.5, pp.1, 2016, https://doi.org/10.1186/s40064-016-2150-4
- EGFR mutation frequency in Middle East and African non-small cell lung cancer patients: a systematic review and meta-analysis vol.18, pp.1, 2018, https://doi.org/10.1186/s12885-018-4774-y
- Clinical significance of serum EGFR gene mutation and serum tumor markers in predicting tyrosine kinase inhibitor efficacy in lung adenocarcinoma pp.1699-3055, 2019, https://doi.org/10.1007/s12094-018-02014-6