Document Type : Original Research


1 School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 Department of Pathology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 Department of Pathology, National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran

5 Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran

6 Tobacco Prevention and Control Research Center, NRITLD, Shahid Beheshti University of Medical Sciences, Tehran, Iran


Background & Objective: Various studies showed the use  of epidermal growth factor receptors (EGFRs) gene mutations in the therapeutic plan of patients with advanced lung cancer. This study aimed to investigate the frequency and types of EGFR gene mutations among Iranian patients with lung adenocarcinoma referred to a specialized lung diseases hospital from 2014 to 2019.
Methods: The data of all patients with lung adenocarcinoma referred to the Molecular Department of Masih Daneshvari Hospital Laboratory (National Research Institute of Tuberculosis and Lung Diseases) from 2014 to 2019 for EGFR mutation tests were collected. Patients' characteristics data and information on  the frequency and types of EGFR gene mutations were obtained from the hospital information system (HIS). The collected data were analyzed using SPSS 25.
Results: A total of 570 individuals (Mean age of 58.74, 51.6% Male) were included  in the study;  113 out of 570 patients  (19.8%)  were diagnosed with gene mutation. In terms of the type of mutation, 65 participants (57%) showed  deletion, 48 patients (42.1%) were diagnosed with replacement, and one (0.9%) case demonstrated  both. Notably, the mutation rate detected among the female patients  was significantly higher than the male ones (P=0.001); in particular, deletion type of mutation was found more among women, although both genders were the same in terms of the replacement frequency. However, the age had no effect on the   mutation in this study (P=0.05).
Conclusion: Among Iranian patients with lung adenocarcinoma, 19.8% harbored  EGFR gene mutation. This mutation was found in association with lung cancer and could affect the patient's therapeutic plan.


  • The frequency of EGFR mutation among 570 Iranian patients with lung adenocarcinoma was 19.8%.
  • The most common type of mutation was "deletion," presented in exon 19.
  • The mutation frequency was significantly higher among females, mainly in exon 19 and deletion form.
  • Different age groups did not affect the mutation, but the mutation rate was notably higher among non-smokers patients.
  • Patients with mutated EGFR gene might benefit from EGFR inhibitor drugs, and as this mutation is not rare among the Iranian population, physicians should consider its evaluation.


Main Subjects

  1. Didkowska J, Wojciechowska U, Mańczuk M, Łobaszewski J. Lung cancer epidemiology: contemporary and future challenges worldwide. Ann Transl Med. 2016;4(8). [DOI:10.21037/atm.2016.03.11] [PMID] [PMCID]
  2. Team NLSTR. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365(5):395-409. [DOI:10.1056/NEJMoa1102873] [PMID] [PMCID]
  3. Yanagisawa K, Shyr Y, Xu BJ, Massion PP, Larsen PH, White BC, et al. Proteomic patterns of tumour subsets in non-small-cell lung cancer. Lancet. 2003;362(9382):433-9. [DOI:10.1016/S0140-6736(03)14068-8]
  4. Brambilla E, Travis WD, Colby T V, Corrin B, Shimosato Y. The new World Health Organization classification of lung tumours. Eur Respir J. 2001;18(6):1059-68. [DOI:10.1183/09031936.01.00275301] [PMID]
  5. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60(5):277-300. [DOI:10.3322/caac.20073] [PMID]
  6. Cataldo VD, Gibbons DL, Pérez-Soler R, Quintás-Cardama A. Treatment of non-small-cell lung cancer with erlotinib or gefitinib. N Engl J Med. 2011;364(10):947-55. [DOI:10.1056/NEJMct0807960] [PMID]
  7. Malhotra J, Malvezzi M, Negri E, La Vecchia C, Boffetta P. Risk factors for lung cancer worldwide. Eur Respir J. 2016;48(3):889-902. [DOI:10.1183/13993003.00359-2016] [PMID]
  8. Yamaguchi T, Shimizu J, Hasegawa T, Horio Y, Inaba Y, Yatabe Y, et al. Pre-existing pulmonary fibrosis is a risk factor for anti-PD-1-related pneumonitis in patients with non-small cell lung cancer: a retrospective analysis. Lung Cancer. 2018;125:212-7. [DOI:10.1016/j.lungcan.2018.10.001] [PMID]
  9. Bernatsky S, Ramsey-Goldman R, Petri M, Urowitz MB, Gladman DD, Fortin PR, et al. Smoking is the most significant modifiable lung cancer risk factor in systemic lupus erythematosus. J Rheumatol. 2018;45(3):393-6. [DOI:10.3899/jrheum.170652] [PMID] [PMCID]
  10. Dalton WS, Friend SH. Cancer biomarkers-an invitation to the table. Science (80- ). 2006;312(5777):1165-8. [DOI:10.1126/science.1125948] [PMID]
  11. Beretta L. Proteomics from the clinical perspective: many hopes and much debate. Nat Methods. 2007;4(10):785-6. [DOI:10.1038/nmeth1007-785] [PMID]
  12. Kang S-M, Sung H-J, Ahn J-M, Park J-Y, Lee S-Y, Park C-S, et al. The Haptoglobin β chain as a supportive biomarker for human lung cancers. Mol Biosyst. 2011;7(4):1167-75. [DOI:10.1039/c0mb00242a] [PMID]
  13. Díaz-Serrano A, Gella P, Jiménez E, Zugazagoitia J, Rodríguez LP-A. Targeting EGFR in lung cancer: current standards and developments. Drugs. 2018;78(9):893-911. [DOI:10.1007/s40265-018-0916-4] [PMID]
  14. Liu Y, Zhang Y, Zhang L, Liu B, Wang Y, Zhou X, et al. Efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors for lung squamous carcinomas harboring EGFR mutation: A multicenter study and pooled analysis of published reports. Oncotarget. 2017;8(30):49680. [DOI:10.18632/oncotarget.17915] [PMID] [PMCID]
  15. Petrini I, Lencioni M, Vasile E, Fornaro L, Belluomini L, Pasquini G, et al. EGFR and AKT1 overexpression are mutually exclusive and associated with a poor survival in resected gastric adenocarcinomas. Cancer Biomarkers. 2018;21(3):731-41. [DOI:10.3233/CBM-170865] [PMID]
  16. Sigismund S, Avanzato D, Lanzetti L. Emerging functions of the EGFR in cancer. Mol Oncol. 2018;12(1):3-20. [DOI:10.1002/1878-0261.12155] [PMID] [PMCID]
  17. Yokoyama T, Kondo M, Goto Y, Fukui T, Yoshioka H, Yokoi K, et al. EGFR point mutation in non‐small cell lung cancer is occasionally accompanied by a second mutation or amplification. Cancer Sci. 2006;97(8):753-9. [DOI:10.1111/j.1349-7006.2006.00233.x] [PMID]
  18. Mammano E, Belluco C, Sciro M, Mencarelli R, Agostini M, Michelotto M, et al. Epidermal growth factor receptor (EGFR): mutational and protein expression analysis in gastric cancer. Anticancer Res. 2006;26(5A):3547-50.
  19. Marchetti A, Martella C, Felicioni L, Barassi F, Salvatore S, Chella A, et al. EGFR mutations in non-small-cell lung cancer: analysis of a large series of cases and development of a rapid and sensitive method for diagnostic screening with potential implications on pharmacologic treatment. J Clin Oncol. 2005;23(4):857-65. [DOI:10.1200/JCO.2005.08.043] [PMID]
  20. Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science (80- ). 2004;304(5676):1497-500. [DOI:10.1126/science.1099314] [PMID]
  21. Mu XL, Li LY, Zhang XT, Wang MZ, Feng RE, Cui QC, et al. Gefitinib-sensitive mutations of the epidermal growth factor receptor tyrosine kinase domain in Chinese patients with non-small cell lung cancer. Clin Cancer Res. 2005;11(12):4289-94. [DOI:10.1158/1078-0432.CCR-04-2506] [PMID]
  22. Yamamoto H, Toyooka S, Mitsudomi T. Impact of EGFR mutation analysis in non-small cell lung cancer. Lung Cancer [Internet]. 2009;63(3):315-21. [DOI:10.1016/j.lungcan.2008.06.021] [PMID]
  23. Offin M, Rizvi H, Tenet M, Ni A, Sanchez-Vega F, Li BT, et al. Tumor mutation burden and efficacy of EGFR-tyrosine kinase inhibitors in patients with EGFR-mutant lung cancers. Clin Cancer Res. 2019;25(3):1063-9. [DOI:10.1158/1078-0432.CCR-18-1102] [PMID] [PMCID]
  24. Basi A, Khaledi F, Niya MHK, Rezvani H, Rakhshani N. Epidermal growth factor receptor mutations in lung adenocarcinomas: A single center study from Iran. Asian Pacific J cancer Prev APJCP. 2018;19(1):111.
  25. Delektorskaya V V, Chemeris GY, Kononets P V, Grigorchuk AY. Clinical significance of hyperexpression of epidermal growth factor receptors (EGFR and HER-2) in esophageal squamous cell carcinoma. Bull Exp Biol Med. 2009;148(2):241. [DOI:10.1007/s10517-009-0659-z] [PMID]
  26. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350(21):2129-39. [DOI:10.1056/NEJMoa040938] [PMID]
  27. Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, et al. 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. 2004;101(36):13306-11. [DOI:10.1073/pnas.0405220101] [PMID] [PMCID]
  28. Moutinho C, Mateus AR, Milanezi F, Carneiro F, Seruca R, Suriano G. Epidermal growth factor receptor structural alterations in gastric cancer. BMC Cancer. 2008;8(1):10. [DOI:10.1186/1471-2407-8-10] [PMID] [PMCID]
  29. Lee JW, Soung YH, Kim SY, Park WS, Nam SW, Kim SH, et al. ERBB2 kinase domain mutation in a gastric cancer metastasis. Apmis. 2005;113(10):683-7. [DOI:10.1111/j.1600-0463.2005.apm_284.x] [PMID]
  30. Lashkarizadeh, M., Bazrafshani, M., Aghaei-Afshar, M., Zahiri, N., Dehghan-Kohestani, S. Prevalence of Nucleotide Alterations of EGFR Gene in Patients with Esophageal Squamous Cell Carcinoma in Kerman. J Kerman Univ Med Sci. 2012; 19(3): 253-9.
  31. Matsuo K, Ito H, Yatabe Y, Hiraki A, Hirose K, Wakai K, et al. Risk factors differ for non‐small‐cell lung cancers with and without EGFR mutation: assessment of smoking and sex by a case‐control study in Japanese. Cancer Sci. 2007;98(1):96-101. [DOI:10.1111/j.1349-7006.2006.00347.x] [PMID]
  32. Tseng C-H, Chiang C-J, Tseng J-S, Yang T-Y, Hsu K-H, Chen K-C, et al. EGFR mutation, smoking, and gender in advanced lung adenocarcinoma. Oncotarget. 2017;8(58):98384. [DOI:10.18632/oncotarget.21842] [PMID] [PMCID]
  33. Duffy MJ. Clinical uses of tumor markers: a critical review. Crit Rev Clin Lab Sci. 2001;38(3):225-62. [DOI:10.1080/20014091084218] [PMID]
  34. Thomas CMG, Sweep CGJ. Serum tumor markers: past, state of the art, and future. Int J Biol Markers. 2001;16(2):73-86. [DOI:10.1177/172460080101600201]
  35. Yang B, Li X, Ren T, Yin Y. Autoantibodies as diagnostic biomarkers for lung cancer: A systematic review. Cell Death Discov. 2019;5(1):1-15. [DOI:10.1038/s41421-018-0068-4] [PMID] [PMCID]
  36. Leighl NB, Page RD, Raymond VM, Daniel DB, Divers SG, Reckamp KL, et al. Clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer. Clin Cancer Res. 2019;25(15):4691-700. [DOI:10.1158/1078-0432.CCR-19-0624] [PMID]
  37. Liang L-B, Zhu W-J, Chen X-M, Luo F-M. Plasma miR-30a-5p as an early novel noninvasive diagnostic and prognostic biomarker for lung cancer. Futur Oncol. 2019;15(32):3711-21. [DOI:10.2217/fon-2019-0393] [PMID]
  38. Oyama T, Kawamoto T, Matsuno K, Osaki T, Matsumoto A, Isse T, et al. A case-case study comparing the usefulness of serum trace elements (Cu, Zn and Se) and tumor markers (CEA, SCC and SLX) in non-small cell lung cancer patients. Anticancer Res. 2003;23(1B):605-12.
  39. Pastor A, Menendez R, Cremades MJ, Pastor V, Llopis R, Aznar J. Diagnostic value of SCC, CEA and CYFRA 21.1 in lung cancer: a Bayesian analysis. Eur Respir J. 1997;10(3):603-9.
  40. Bates J, Rutherford R, Divilly M, Finn J, Grimes H, O'Muircheartaigh I, et al. Clinical value of CYFRA 21.1, carcinoembryonic antigen, neurone-specific enolase, tissue polypeptide specific antigen and tissue polypeptide antigen in the diagnosis of lung cancer. Eur Respir J. 1997;10(11):2535-8. [DOI:10.1183/09031936.97.10112535] [PMID]