Skip to main content

Advertisement

SpringerLink
Log in

EGFR mutation status in brain metastases of non-small cell lung carcinoma

  • Topic Review
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Brain metastases are a frequent and grave complication of non-small cell lung carcinoma (NSCLC). The prognosis is generally poor, despite standard therapy based on surgery and radiotherapy. A degree of understanding of the molecular basis of tumors has led to the development of targeted agents with promising initial findings for the treatment of NSCLC. EGFR mutations have been identified which are associated with significant sensitivity to EGFR tyrosine kinase inhibitors (TKI) and correlate with improved outcome in patients with NSCLC who are treated with these agents. The adoption of treatment tailored to the genetic make-up of individual tumors could lead to substantial therapeutic improvements, and such targeted therapy might be considered as a therapeutic option for brain metastases in the future. We review current knowledge about EGFR mutation status in the specific context of brain metastasis: its association with the response of brain metastases to TKI, its prevalence in brain metastases, and the correlation between mutation status in metastases as compared to the corresponding primary lung carcinoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Nathoo N, Chahlavi A, Barnett GH, Toms SA (2005) Pathobiology of brain metastases. J Clin Pathol 3:237–242

    Article  Google Scholar 

  2. Santarelli JG, Sarkissian V, Hou LC, Veeravagu A, Tse V (2007) Molecular events of brain metastasis. Neurosurg Focus 3:E1

    Article  Google Scholar 

  3. Eichler AF, Chung E, Kodack DP, Loeffler JS, Fukumura D, Jain RK (2011) The biology of brain metastases-translation to new therapies. Nat Rev Clin Oncol 6:344–356

    Google Scholar 

  4. Cox JD, Scott CB, Byhardt RW, Emami B, Russell AH, Fu KK et al (1999) Addition of chemotherapy to radiation therapy alters failure patterns by cell type within non-small cell carcinoma of lung (NSCCL): analysis of radiation therapy oncology group (RTOG) trials. Int J Radiat Oncol Biol Phys 3:505–509

    Article  Google Scholar 

  5. Maghfoor I, Perry MC (1998) Lung cancer. In: Hazzard W, Andres R, Bierman E (eds) Principles of geriatric medicine and gerontology, 4th edn. McGraw-Hill, New York

    Google Scholar 

  6. Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T et al (1997) Recursive partitioning analysis (RPA) of prognostic factors in three radiation therapy oncology group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 4:745–751

    Article  Google Scholar 

  7. Langer CJ, Mehta MP (2005) Current management of brain metastases, with a focus on systemic options. J Clin Oncol 25:6207–6219

    Article  Google Scholar 

  8. Sundstrom JT, Minn H, Lertola KK, Nordman E (1998) Prognosis of patients treated for intracranial metastases with whole-brain irradiation. Ann Med 3:296–299

    Article  Google Scholar 

  9. Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC et al (2004) Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet 9422:1665–1672

    Article  Google Scholar 

  10. Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ et al (1990) A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 8:494–500

    Article  Google Scholar 

  11. Vecht CJ, Haaxma-Reiche H, Noordijk EM, Padberg GW, Voormolen JH, Hoekstra FH et al (1993) Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery? Ann Neurol 6:583–590

    Article  Google Scholar 

  12. Ushio Y, Arita N, Hayakawa T, Mogami H, Hasegawa H, Bitoh S et al (1991) Chemotherapy of brain metastases from lung carcinoma: a controlled randomized study. Neurosurgery 2:201–205

    Google Scholar 

  13. Cortes J, Rodriguez J, Aramendia JM, Salgado E, Gurpide A, Garcia-Foncillas J et al (2003) Front-line paclitaxel/cisplatin-based chemotherapy in brain metastases from non-small-cell lung cancer. Oncology 1:28–35

    Article  Google Scholar 

  14. Paz-Ares L, Soulieres D, Melezinek I, Moecks J, Keil L, Mok T et al (2010) Clinical outcomes in non-small-cell lung cancer patients with EGFR mutations: pooled analysis. J Cell Mol Med 1–2:51–69

    Article  Google Scholar 

  15. Rosell R, Moran T, Queralt C, Porta R, Cardenal F, Camps C et al (2009) Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 10:958–967

    Article  Google Scholar 

  16. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW 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 21:2129–2139

    Article  Google Scholar 

  17. Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N et al (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 10:947–957

    Article  Google Scholar 

  18. Sharma SV, Bell DW, Settleman J, Haber DA (2007) Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 3:169–181

    Article  Google Scholar 

  19. Shigematsu H, Lin L, Takahashi T, Nomura M, Suzuki M, Wistuba II et al (2005) Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 5:339–346

    Article  Google Scholar 

  20. Tanaka T, Matsuoka M, Sutani A, Gemma A, Maemondo M, Inoue A et al (2010) Frequency of and variables associated with the EGFR mutation and its subtypes. Int J Cancer 3:651–655

    Article  Google Scholar 

  21. Sanders HR, Albitar M (2010) Somatic mutations of signaling genes in non-small-cell lung cancer. Cancer Genet Cytogenet 1:7–15

    Article  Google Scholar 

  22. Sartori G, Cavazza A, Sgambato A, Marchioni A, Barbieri F, Longo L et al (2009) EGFR and K-ras mutations along the spectrum of pulmonary epithelial tumors of the lung and elaboration of a combined clinicopathologic and molecular scoring system to predict clinical responsiveness to EGFR inhibitors. Am J Clin Pathol 4:478–489

    Article  Google Scholar 

  23. Gately K, O’Flaherty J, Cappuzzo F, Pirker R, Kerr K, O’Byrne K (2012) The role of the molecular footprint of EGFR in tailoring treatment decisions in NSCLC. J Clin Pathol 1:1–7

    Article  Google Scholar 

  24. Pao W, Ladanyi M (2007) Epidermal growth factor receptor mutation testing in lung cancer: searching for the ideal method. Clin Cancer Res 17:4954–4955

    Article  Google Scholar 

  25. Matsumoto S, Takahashi K, Iwakawa R, Matsuno Y, Nakanishi Y, Kohno T et al (2006) Frequent EGFR mutations in brain metastases of lung adenocarcinoma. Int J Cancer 6:1491–1494

    Article  Google Scholar 

  26. Gow CH, Chang YL, Hsu YC, Tsai MF, Wu CT, Yu CJ et al (2009) Comparison of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in tyrosine kinase inhibitor-naive non-small-cell lung cancer. Ann Oncol 4:696–702

    Article  Google Scholar 

  27. Huang SF, Liu HP, Li LH, Ku YC, Fu YN, Tsai HY 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 24:8195–8203

    Article  Google Scholar 

  28. Wu YL, Zhong WZ, Li LY, Zhang XT, Zhang L, Zhou CC 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 5:430–439

    Article  Google Scholar 

  29. Cortot AB, Italiano A, Burel-Vandenbos F, Martel-Planche G, Hainaut P (2010) KRAS mutation status in primary nonsmall cell lung cancer and matched metastases. Cancer 11:2682–2687

    Article  Google Scholar 

  30. Daniele L, Cassoni P, Bacillo E, Cappia S, Righi L, Volante M et al (2009) Epidermal growth factor receptor gene in primary tumor and metastatic sites from non-small cell lung cancer. J Thorac Oncol 6:684–688

    Article  Google Scholar 

  31. Sun M, Behrens C, Feng L, Ozburn N, Tang X, Yin G et al (2009) HER family receptor abnormalities in lung cancer brain metastases and corresponding primary tumors. Clin Cancer Res 15:4829–4837

    Article  PubMed  CAS  Google Scholar 

  32. Gazdar AF (2009) Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene S24-31

  33. Marchetti A, Martella C, Felicioni L, Barassi F, Salvatore S, Chella A et al (2005) 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 4:857–865

    Article  Google Scholar 

  34. Li Z, Guo H (2011) The retrospective analysis of the frequency of EGFR mutations and efficacy of gefitinib in NSCLC patients with brain metastases. J Clin Oncol 29 (Suppl abstr e18065)

  35. Eichler AF, Kahle KT, Wang DL, Joshi VA, Willers H, Engelman JA et al (2010) EGFR mutation status and survival after diagnosis of brain metastasis in nonsmall cell lung cancer. Neuro Oncol 11:1193–1199

    Article  Google Scholar 

  36. Heon S, Yeap BY, Britt GJ, Costa DB, Rabin MS, Jackman DM et al (2010) Development of central nervous system metastases in patients with advanced non-small cell lung cancer and somatic EGFR mutations treated with gefitinib or erlotinib. Clin Cancer Res 23:5873–5882

    Article  Google Scholar 

  37. Sekine A, Kato T, Hagiwara E, Shinohara T, Komagata T, Iwasawa T et al (2012) Metastatic brain tumors from non-small cell lung cancer with EGFR mutations: distinguishing influence of exon 19 deletion on radiographic features. Lung Cancer 1:64–69

    Article  Google Scholar 

  38. Heimberger AB, Learn CA, Archer GE, McLendon RE, Chewning TA, Tuck FL et al (2002) Brain tumors in mice are susceptible to blockade of epidermal growth factor receptor (EGFR) with the oral, specific, EGFR-tyrosine kinase inhibitor ZD1839 (iressa). Clin Cancer Res 11:3496–3502

    Google Scholar 

  39. Gounant V, Wislez M, Poulot V, Khalil A, Lavole A, Cadranel J et al (2007) Subsequent brain metastasis responses to epidermal growth factor receptor tyrosine kinase inhibitors in a patient with non-small-cell lung cancer. Lung Cancer 3:425–428

    Article  Google Scholar 

  40. Popat S, Hughes S, Papadopoulos P, Wilkins A, Moore S, Priest K et al (2007) Recurrent responses to non-small cell lung cancer brain metastases with erlotinib. Lung Cancer 1:135–137

    Article  Google Scholar 

  41. Fekrazad MH, Ravindranathan M, Jones DV Jr (2007) Response of intracranial metastases to erlotinib therapy. J Clin Oncol 31:5024–5026

    Article  Google Scholar 

  42. Cappuzzo F, Ardizzoni A, Soto-Parra H, Gridelli C, Maione P, Tiseo M et al (2003) Epidermal growth factor receptor targeted therapy by ZD 1839 (Iressa) in patients with brain metastases from non-small cell lung cancer (NSCLC). Lung Cancer 2:227–231

    Article  Google Scholar 

  43. Shimato S, Mitsudomi T, Kosaka T, Yatabe Y, Wakabayashi T, Mizuno M et al (2006) EGFR mutations in patients with brain metastases from lung cancer: association with the efficacy of gefitinib. Neuro Oncol 2:137–144

    Article  Google Scholar 

  44. Namba Y, Kijima T, Yokota S, Niinaka M, Kawamura S, Iwasaki T et al (2004) Gefitinib in patients with brain metastases from non-small-cell lung cancer: review of 15 clinical cases. Clin Lung Cancer 2:123–128

    Article  Google Scholar 

  45. Jamal-Hanjani M, Spicer J (2012) Epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of epidermal growth factor receptor-mutant non-small cell lung cancer metastatic to the brain. Clin Cancer Res 4:938–944

    Article  Google Scholar 

  46. Wu C, Li YL, Wang ZM, Li Z, Zhang TX, Wei Z (2007) Gefitinib as palliative therapy for lung adenocarcinoma metastatic to the brain. Lung Cancer 3:359–364

    Article  Google Scholar 

  47. Kim JE, Lee DH, Choi Y, Yoon DH, Kim SW, Suh C et al (2009) Epidermal growth factor receptor tyrosine kinase inhibitors as a first-line therapy for never-smokers with adenocarcinoma of the lung having asymptomatic synchronous brain metastasis. Lung Cancer 3:351–354

    Article  Google Scholar 

  48. Ceresoli GL, Cappuzzo F, Gregorc V, Bartolini S, Crino L, Villa E (2004) Gefitinib in patients with brain metastases from non-small-cell lung cancer: a prospective trial. Ann Oncol 7:1042–1047

    Article  Google Scholar 

  49. Hotta K, Kiura K, Ueoka H, Tabata M, Fujiwara K, Kozuki T et al (2004) Effect of gefitinib (‘Iressa’, ZD1839) on brain metastases in patients with advanced non-small-cell lung cancer. Lung Cancer 2:255–261

    Article  Google Scholar 

  50. Porta R, Sanchez-Torres JM, Paz-Ares L, Massuti B, Reguart N, Mayo C et al (2011) Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation. Eur Respir J 3:624–631

    Article  Google Scholar 

  51. Omuro AM, Kris MG, Miller VA, Franceschi E, Shah N, Milton DT et al (2005) High incidence of disease recurrence in the brain and leptomeninges in patients with nonsmall cell lung carcinoma after response to gefitinib. Cancer 11:2344–2348

    Article  Google Scholar 

  52. Elmeliegy MA, Carcaboso AM, Tagen M, Bai F, Stewart CF (2011) Role of ATP-binding cassette and solute carrier transporters in erlotinib CNS penetration and intracellular accumulation. Clin Cancer Res 1:89–99

    Article  Google Scholar 

  53. Weber B, Winterdahl M, Memon A, Sorensen BS, Keiding S, Sorensen L et al (2011) Erlotinib accumulation in brain metastases from non-small cell lung cancer: visualization by positron emission tomography in a patient harboring a mutation in the epidermal growth factor receptor. J Thorac Oncol 7:1287–1289

    Article  Google Scholar 

  54. Jackman DM, Holmes AJ, Lindeman N, Wen PY, Kesari S, Borras AM et al (2006) Response and resistance in a non-small-cell lung cancer patient with an epidermal growth factor receptor mutation and leptomeningeal metastases treated with high-dose gefitinib. J Clin Oncol 27:4517–4520

    Article  Google Scholar 

  55. Clarke JL, Pao W, Wu N, Miller VA, Lassman AB (2010) High dose weekly erlotinib achieves therapeutic concentrations in CSF and is effective in leptomeningeal metastases from epidermal growth factor receptor mutant lung cancer. J Neurooncol 2:283–286

    Article  Google Scholar 

  56. Masuda T, Hattori N, Hamada A, Iwamoto H, Ohshimo S, Kanehara M et al (2011) Erlotinib efficacy and cerebrospinal fluid concentration in patients with lung adenocarcinoma developing leptomeningeal metastases during gefitinib therapy. Cancer Chemother Pharmacol 6:1465–1469

    Article  Google Scholar 

  57. Togashi Y, Masago K, Fukudo M, Tsuchido Y, Okuda C, Kim YH et al (2011) Efficacy of increased-dose erlotinib for central nervous system metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation. Cancer Chemother Pharmacol 4:1089–1092

    Article  Google Scholar 

  58. Hata A, Kaji R, Fujita S, Katakami N (2011) High-dose erlotinib for refractory brain metastases in a patient with relapsed non-small cell lung cancer. J Thorac Oncol 3:653–654

    Article  Google Scholar 

  59. Grommes C, Oxnard GR, Kris MG, Miller VA, Pao W, Holodny AI et al (2011) “Pulsatile” high-dose weekly erlotinib for CNS metastases from EGFR mutant non-small cell lung cancer. Neuro Oncol 12:1364–1369

    Article  Google Scholar 

  60. Dhruva N, Socinski MA (2009) Carcinomatous meningitis in non-small-cell lung cancer: response to high-dose erlotinib. J Clin Oncol 22:e31–e32

    Article  Google Scholar 

  61. Xu Y, Lin N, Yu Y, Fang L, Sun X and Jiang H (2011) Cerebrospinal fluid concentration of gefitinib in patients with central nervous system metastases of non-small cell lung cancer. J Thorac Oncol: S659–S660

  62. Morris PG, Reiner AS, Szenberg OR, Clarke JL, Panageas KS, Perez HR et al (2012) Leptomeningeal metastasis from non-small cell lung cancer: survival and the impact of whole brain radiotherapy. J Thorac Oncol 2:382–385

    Article  Google Scholar 

  63. Yi HG, Kim HJ, Kim YJ, Han SW, Oh DY, Lee SH et al (2009) Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective for leptomeningeal metastasis from non-small cell lung cancer patients with sensitive EGFR mutation or other predictive factors of good response for EGFR TKI. Lung Cancer 1:80–84

    Article  Google Scholar 

  64. de Vries NA, Buckle T, Zhao J, Beijnen JH, Schellens JH, van Tellingen O (2012) Restricted brain penetration of the tyrosine kinase inhibitor erlotinib due to the drug transporters P-gp and BCRP. Invest New Drugs 2:443–449

    Article  Google Scholar 

  65. Fukuhara T, Saijo Y, Sakakibara T, Inoue A, Morikawa N, Kanamori M et al (2008) Successful treatment of carcinomatous meningitis with gefitinib in a patient with lung adenocarcinoma harboring a mutated EGF receptor gene. Tohoku J Exp Med 4:359–363

    Article  Google Scholar 

  66. Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF et al (2005) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 3:e73

    Article  Google Scholar 

  67. Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO et al (2007) MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 5827:1039–1043

    Article  Google Scholar 

  68. Bean J, Riely GJ, Balak M, Marks JL, Ladanyi M, Miller VA et al (2008) Acquired resistance to epidermal growth factor receptor kinase inhibitors associated with a novel T854A mutation in a patient with EGFR-mutant lung adenocarcinoma. Clin Cancer Res 22:7519–7525

    Article  Google Scholar 

  69. Balak MN, Gong Y, Riely GJ, Somwar R, Li AR, Zakowski MF et al (2006) Novel D761Y and common secondary T790 M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin Cancer Res 21:6494–6501

    Article  Google Scholar 

  70. Guix M, Faber AC, Wang SE, Olivares MG, Song Y, Qu S et al (2008) Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins. J Clin Invest 7:2609–2619

    Google Scholar 

  71. Katayama T, Shimizu J, Suda K, Onozato R, Fukui T, Ito S et al (2009) Efficacy of erlotinib for brain and leptomeningeal metastases in patients with lung adenocarcinoma who showed initial good response to gefitinib. J Thorac Oncol 11:1415–1419

    Article  Google Scholar 

  72. Benedettini E, Sholl LM, Peyton M, Reilly J, Ware C, Davis L et al (2010) Met activation in non-small cell lung cancer is associated with de novo resistance to EGFR inhibitors and the development of brain metastasis. Am J Pathol 1:415–423

    Article  Google Scholar 

  73. Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 5676:1497–1500

    Article  Google Scholar 

  74. Italiano A, Vandenbos FB, Otto J, Mouroux J, Fontaine D, Marcy PY et al (2006) Comparison of the epidermal growth factor receptor gene and protein in primary non-small-cell-lung cancer and metastatic sites: implications for treatment with EGFR-inhibitors. Ann Oncol 6:981–985

    Article  Google Scholar 

  75. Gomez-Roca C, Raynaud CM, Penault-Llorca F, Mercier O, Commo F, Morat L et al (2009) Differential expression of biomarkers in primary non-small cell lung cancer and metastatic sites. J Thorac Oncol 10:1212–1220

    Article  Google Scholar 

  76. Sun L, Zhang Q, Luan H, Zhan Z, Wang C, Sun B (2011) Comparison of KRAS and EGFR gene status between primary non-small cell lung cancer and local lymph node metastases: implications for clinical practice. J Exp Clin Cancer Res 30:30

    Google Scholar 

  77. Park S, Holmes-Tisch AJ, Cho EY, Shim YM, Kim J, Kim HS et al (2009) Discordance of molecular biomarkers associated with epidermal growth factor receptor pathway between primary tumors and lymph node metastasis in non-small cell lung cancer. J Thorac Oncol 7:809–815

    Article  Google Scholar 

  78. Chang YL, Wu CT, Shih JY, Lee YC (2011) Comparison of p53 and epidermal growth factor receptor gene status between primary tumors and lymph node metastases in non-small cell lung cancers. Ann Surg Oncol 2:543–550

    Article  Google Scholar 

  79. Han CB, Ma JT, Li F, Zhao JZ, Jing W, Zhou Y et al (2012) EGFR and KRAS mutations and altered c-Met gene copy numbers in primary non-small cell lung cancer and associated stage N2 lymph node-metastasis. Cancer Lett 1:63–72

    Article  Google Scholar 

  80. Han HS, Eom DW, Kim JH, Kim KH, Shin HM, An JY et al (2011) EGFR mutation status in primary lung adenocarcinomas and corresponding metastatic lesions: discordance in pleural metastases. Clin Lung Cancer 6:380–386

    Article  Google Scholar 

  81. Schmid K, Oehl N, Wrba F, Pirker R, Pirker C, Filipits M (2009) EGFR/KRAS/BRAF mutations in primary lung adenocarcinomas and corresponding locoregional lymph node metastases. Clin Cancer Res 14:4554–4560

    Article  Google Scholar 

  82. Munfus-McCray D, Harada S, Adams C, Askin F, Clark D, Gabrielson E et al (2011) EGFR and KRAS mutations in metastatic lung adenocarcinomas. Hum Pathol 10:1447–1453

    Article  Google Scholar 

  83. Kalikaki A, Koutsopoulos A, Trypaki M, Souglakos J, Stathopoulos E, Georgoulias V et al (2008) Comparison of EGFR and K-RAS gene status between primary tumours and corresponding metastases in NSCLC. Br J Cancer 6:923–929

    Article  Google Scholar 

  84. Fang Q, Zhang L, Wang S, Ou W (2011) Discordance of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in non-small cell lung cancer. Zhongguo Fei Ai Za Zhi 6:518–522

    Google Scholar 

  85. Han C, Zou H, Ma J, Zhou Y, Zhao J (2010) Comparison of EGFR and KRAS status between primary non-small cell lung cancer and corresponding metastases: a systematic review and meta-analysis. Zhongguo Fei Ai Za Zhi 9:882–891

    Google Scholar 

  86. Ruppert AM, Beau-Faller M, Neuville A, Guerin E, Voegeli AC, Mennecier B et al (2009) EGFR-TKI and lung adenocarcinoma with CNS relapse: interest of molecular follow-up. Eur Respir J 2:436–440

    Google Scholar 

Download references

Conflict of interest

None

Author information

Authors and Affiliations

  1. Department of Pathology, University Hospital of Nice, Nice, France

    Fanny Burel-Vandenbos & Damien Ambrosetti

  2. INSERM U898/UNSA Stem Cells, Cancer and Development, University of Nice Sophia-Antipolis, Nice, France

    Fanny Burel-Vandenbos

  3. Institute of Research on Cancer and Ageing in Nice, University of Nice Sophia-Antipolis, Nice, France

    Damien Ambrosetti

  4. Department of Pathology, West Kent Oncology Centre, Maidstone Hospital, Kent, UK

    Michael Coutts

  5. Genetics of Solid Tumours, Faculty of Medicine, University of Nice Sophia-Antipolis, Nice, France

    Florence Pedeutour

  6. Laboratoire Central d’Anatomie Pathologique, Hopital Pasteur, 30 Voie Romaine, 06000, Nice, France

    Fanny Burel-Vandenbos

Authors
  1. Fanny Burel-Vandenbos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Damien Ambrosetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael Coutts
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Florence Pedeutour
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fanny Burel-Vandenbos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Burel-Vandenbos, F., Ambrosetti, D., Coutts, M. et al. EGFR mutation status in brain metastases of non-small cell lung carcinoma. J Neurooncol 111, 1–10 (2013). https://doi.org/10.1007/s11060-012-0990-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-012-0990-5

Keywords

Search

Navigation