DOI QR코드

DOI QR Code

Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancers in a Multiethnic Malaysian Patient Population

  • Liam, Chong-Kin ;
  • Leow, Hwong-Ruey ;
  • How, Soon-Hin ;
  • Pang, Yong-Kek ;
  • Chua, Keong-Tiong ;
  • Lim, Boon-Khaw ;
  • Lai, Nai-Lang ;
  • Kuan, Yeh-Chunn ;
  • Pailoor, Jayalakshmi ;
  • Rajadurai, Pathmanathan
  • Published : 2014.01.15

Abstract

Background: Mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) are predictive of response to EGFR-targeted therapy in advanced stages of disease. This study aimed to determine the frequency of EGFR mutations in NSCLCs and to correlate their presence with clinical characteristics in multiethnic Malaysian patients. Materials and Methods: In this prospective study, EGFR mutations in exons 18, 19, 20 and 21 in formalin-fixed paraffin-embedded biopsy specimens of consecutive NSCLC patients were asessed by real-time polymerase chain reaction. Results: EGFR mutations were detected in NSCLCs from 55 (36.4%) of a total of 151 patients, being significantly more common in females (62.5%) than in males (17.2%) [odds ratio (OR), 8.00; 95% confidence interval (CI), 3.77-16.98; p<0.001] and in never smokers (62.5%) than in ever smokers (12.7%) (OR, 11.50; 95%CI, 5.08-26.03; p<0.001). Mutations were more common in adenocarcinoma (39.4%) compared to non-adenocarcinoma NSCLCs (15.8%) (p=0.072). The mutation rates in patients of different ethnicities were not significantly different (p=0.08). Never smoking status was the only clinical feature that independently predicted the presence of EGFR mutations (adjusted OR, 5.94; 95%CI, 1.94-18.17; p=0.002). Conclusions: In Malaysian patients with NSCLC, the EGFR mutation rate was similar to that in other Asian populations. EGFR mutations were significantly more common in female patients and in never smokers. Never smoking status was the only independent predictor for the presence of EGFR mutations.

Keywords

EGFR mutation;multiethnic;non-small cell lung cancer;smoking;Malaysian

References

  1. Kimura H, Fujiwara Y, Sone T, et al (2006). High sensitivity detection of epidermal growth factor receptor mutations in the pleural effusion of non-small cell lung cancer patients. Cancer Sci, 97, 642-8. https://doi.org/10.1111/j.1349-7006.2006.00216.x
  2. Huang SF, Liu HP, Li LH, et al (2004). High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan. Clin Cancer Res, 10, 8195-203. https://doi.org/10.1158/1078-0432.CCR-04-1245
  3. Huang YS, Yang JJ, Zhang XC, et al (2011). Impact of smoking status and pathologic type on epidermal growth factor receptor mutations in lung cancer. Chin Med J, 124, 2457-60.
  4. Jemal A, Siegel R, Ward E, et al (2006). Cancer statistics, 2006. CA Cancer J Clin, 56, 106-30. https://doi.org/10.3322/canjclin.56.2.106
  5. Kosaka T, Yatabe Y, Endoh H, et al (2004). Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Res, 64, 8919-23. https://doi.org/10.1158/0008-5472.CAN-04-2818
  6. Li C, Fang R, Sun Y, et al (2011). Spectrum of oncogenic driver mutations in lung adenocarcinomas from East Asian never smokers. PLoS One, 6, 28204. https://doi.org/10.1371/journal.pone.0028204
  7. Liam CK, Pang YK, Leow CH, Shyamala P, Menon AA (2006). Changes in the distribution of lung cancer cell types and patient demography in a developing multiracial Asian country. Lung Cancer, 53, 23-30. https://doi.org/10.1016/j.lungcan.2006.03.009
  8. Liang Z, Zhang J, Zeng X, et al (2010). Relationship between EGFR expression, copy number and mutation in lung adenocarcinomas. BMC Cancer, 10, 376. https://doi.org/10.1186/1471-2407-10-376
  9. Cortes-Funes H, Gomez C, Rosell R, et al (2005). Epidermal growth factor receptor activating mutations in Spanish gefitinib-treated non-small cell lung cancer patients. Ann Oncol, 16, 1081-6. https://doi.org/10.1093/annonc/mdi221
  10. QIAamp (R) DNA FFPE Tissue Handbook for purification of genomic DNA from formalin-fixed, paraffin-embedded tissues 10/2007.
  11. Rivera MP, Detterbeck FC, Loomis DP (2001). Epidemiology and classification of lung cancer. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenma JG, editors. Diagnosis and treatment of lung cancer. 1st ed. Philadelphia: WB Saunders Co, 45-72.
  12. 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
  13. Arrieta O, Cardona AF, Federico Bramuglia G, 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
  14. Baik CS, Pritchard CC, Eaton KD, Chow LQ (2013). EGFR mutations in squamous cell lung cancer in never-smokers. J Thorac Oncol, 8, 6-7. https://doi.org/10.1097/JTO.0b013e318274a7dc
  15. Department of Statistics, Malaysia. Population Distribution and Basic Demographic Characteristics: Population and Housing Census of Malaysia 2010..
  16. Ebbert JO, Yang P, Vachon CM, et al (2003) Lung cancer risk reduction after smoking cessation: observations from a prospective cohort of women. J Clin Oncol, 21, 921-6. https://doi.org/10.1200/JCO.2003.05.085
  17. EGFR RGQ PCR Kit Handbook for qualitative measurement of 29 somatic mutations in the EGFR oncogene.06/2011.
  18. QIAGEN Manchester Ltd, Skelton House, Lloyd Street. Han S-W, Kim T-Y, Hwang PG, et al (2005). Predictive and prognostic impact of epidermal growth factor receptor mutation in non-small cell lung cancer patients treated with gefitinib. J Clin Oncol, 23, 2493-501. https://doi.org/10.1200/JCO.2005.01.388
  19. Herbst RS, Heymach JV, Lippman SM (2008). Lung cancer. N Engl J Med, 359, 1367-80. https://doi.org/10.1056/NEJMra0802714
  20. Oken MM, Creech RH, Tormey DC, et al (1982). Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol, 5, 649-55. https://doi.org/10.1097/00000421-198212000-00014
  21. Maheswaran S, Sequist LV, Nagrath S, et al (2008). Detection of mutations in EGFR in circulating lung-cancer cells. Engl J Med, 359, 366-77. https://doi.org/10.1056/NEJMoa0800668
  22. 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
  23. 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
  24. Paez JG, Janne PA, Lee JC, et al (2004). EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science, 304, 1497-500. https://doi.org/10.1126/science.1099314
  25. Paik PK, Varghese AM, Sima CS, et al (2012). Response to erlotinib in patients with EGFR mutant advanced nonsmall cell lung cancers with a squamous or squamous-like component. Mol Cancer Ther, 11, 2535-40. https://doi.org/10.1158/1535-7163.MCT-12-0163
  26. Pallis AG, Voutsina A, Kalikaki A, et al (2007). 'Classical' but not 'other' mutations of EGFR kinase domain are associated with clinical outcome in gefitinib-treated patients with non-small cell lung cancer. Br J Cancer, 11, 1560-6.
  27. Parkin DM, Bray F, Ferlay J, Pisani P (2005). Global cancer statistics, 2002. CA Cancer J Clin, 55, 74-108. https://doi.org/10.3322/canjclin.55.2.74
  28. Perez-Moreno P, Brambilla E, Thomas R, Soria JC (2012). Squamous cell carcinoma of the lung: molecular subtypes and therapeutic opportunities. Clin Cancer Res, 18, 2443-51. https://doi.org/10.1158/1078-0432.CCR-11-2370
  29. Peter Goldstraw (2009). The 7th Edition of TNM in Lung Cancer: What Now? J Thorac Oncol, 4, 671-673. https://doi.org/10.1097/JTO.0b013e31819e7814
  30. Wang J, Ramakrishnan R, Tang Z, et al (2010). Quantifying EGFR alterations in the lung cancer genome with nanofluidic digital PCR arrays. Clin Chem, 56, 623-32. https://doi.org/10.1373/clinchem.2009.134973
  31. Third Report of the National Cancer Registry, Cancer incidence in Malaysia, 2003-2005, National Cancer Registry, Malaysia (http://www.crc.gov.my/ncr).
  32. Vital statistics Malaysia (2005). Department of Statistics, Malaysia 2006.
  33. Wagenknecht LE, Cutter GR, Haley NJ, et al (1990). Racial differences in serum cotinine levels among smokers in the coronary artery risk development in (young) adults study. Am J Public Health, 80, 1053-6. https://doi.org/10.2105/AJPH.80.9.1053
  34. 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
  35. Salto-Tellez M, Tsao MS, Shih JY, et al (2011). Clinical and testing protocols for the analysis of epidermal growth factor receptor mutations in East Asian patients with non-small cell lung cancer. A Combined Clinical-Molecular Pathological Approach. J Thorac Oncol, 6, 1663-9. https://doi.org/10.1097/JTO.0b013e318227816a
  36. Lindeman NI, Cagle PT, Beasley MB, et al (2013). Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Thorac Oncol, 8, 823-59. https://doi.org/10.1097/JTO.0b013e318290868f
  37. Lund-Iversen M, Kleinberg L, Fjellbirkeland L, Helland A, Brustugun OT (2012). Clinicopathological characteristics of 11 NSCLC patients with EGFR-exon 20 mutations. J Thorac Oncol, 7, 1471-3. https://doi.org/10.1097/JTO.0b013e3182614a9d
  38. 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
  39. Sonobe M, Manabe T, Wada H, Tanaka F (2005). Mutations in the epidermal growth factor receptor gene are linked to smoking-independent, lung adenocarcinoma. Br J Cancer, 93, 355-63. https://doi.org/10.1038/sj.bjc.6602707
  40. Sequist LV, Heist RS, Shaw AT, et al (2011). Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice. Ann Oncol, 22, 2616-24. https://doi.org/10.1093/annonc/mdr489
  41. Sharma SV, Bell DW, Settleman J, Haber DA (2007). Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer, 7, 169-81. https://doi.org/10.1038/nrc2088
  42. Shigematsu H, Lin L, Takahashi T, et al (2005). Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst, 97, 339-46. https://doi.org/10.1093/jnci/dji055
  43. Sun YH, Fang R, Gao B, et al (2010). Comparable rate of EGFR kinase domain mutation in lung adenocarcinomas from Chinese male and female never-smokers. Acta Pharmacol Sin, 31, 647-8. https://doi.org/10.1038/aps.2010.43
  44. Sun PL, Seol H, Lee HJ, et al (2012). High incidence of EGFR mutations in Korean men smokers with no intratumoral heterogeneity of lung adenocarcinomas: correlation with histologic subtypes, EGFR/TTF-1 expressions, and clinical features. J Thorac Oncol, 7, 323-30. https://doi.org/10.1097/JTO.0b013e3182381515
  45. Takano T, Ohe Y, Sakamoto H, et al (2005). Epidermal growth factor receptor gene mutations and increased copy numbers predict gefitinib sensitivity in patients with recurrent nonsmall cell lung cancer. J Clin Oncol, 23, 6829-37. https://doi.org/10.1200/JCO.2005.01.0793
  46. Taron M, Ichinose Y, Rosell R, et al (2005). Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinibtreated chemorefractory lung adenocarcinomas. Clin Cancer Res, 11, 5878-85. https://doi.org/10.1158/1078-0432.CCR-04-2618

Cited by

  1. RTN4 3'-UTR Insertion/Deletion Polymorphism and Susceptibility to Non-Small Cell Lung Cancer in Chinese Han Population vol.15, pp.13, 2014, https://doi.org/10.7314/APJCP.2014.15.13.5249
  2. Therapeutic Effects and Adverse Drug Reactions are Affected by Icotinib Exposure and CYP2C19 and EGFR Genotypes in Chinese Non-Small Cell Lung Cancer Patients vol.15, pp.17, 2014, https://doi.org/10.7314/APJCP.2014.15.17.7195
  3. Analysis of CEA Expression and EGFR Mutation Status in Non-small Cell Lung Cancers vol.15, pp.8, 2014, https://doi.org/10.7314/APJCP.2014.15.8.3451
  4. Frequency of EGFR Mutations in Non-small Cell Lung Cancer Patients: Screening Data from West Siberia vol.16, pp.2, 2015, https://doi.org/10.7314/APJCP.2015.16.2.689
  5. Prevalence and Clinical Profile of EGFR Mutation In Non-Small-Cell Lung Carcinoma Patients in Southwest China vol.17, pp.3, 2016, https://doi.org/10.7314/APJCP.2016.17.3.965
  6. Gefitinib as first line therapy in Malaysian patients with EGFR mutation-positive non-small-cell lung cancer: A single-center retrospective study vol.11, pp.4, 2016, https://doi.org/10.3892/ol.2016.4322
  7. Pan-Asian adapted Clinical Practice Guidelines for the management of patients with metastatic non-small-cell lung cancer: a CSCO–ESMO initiative endorsed by JSMO, KSMO, MOS, SSO and TOS vol.30, pp.2, 2018, https://doi.org/10.1093/annonc/mdy554