Skip to main content

Advertisement

SpringerLink
Log in

Prognostic value of epidermal growth factor receptor mutations and histologic subtypes with lung adenocarcinoma

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

The epidermal growth factor receptor (EGFR) mutation status has become one of the most important factors in the treatment of non-small cell lung cancer. However, the relationship between EGFR mutation and the histologic subtype of lung adenocarcinoma remains to be fully elucidated. We examined the relationship between the predominant subtype of adenocarcinoma and the prognosis and investigated the correlation between a new subtype of adenocarcinoma and EGFR mutations. This study included 182 patients with adenocarcinoma who underwent complete resection. The rate of EGFR mutation-positive patients was significantly higher among female patients, never smokers, patients with small tumors (< 3 cm in size), patients with well-differentiated tumors, and patients with a pStage I classification. The rates of adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and lepidic-predominant subtype were high in male EGFR mutation-positive patients. The prevalence of the acinar and papillary-predominant subtypes was high among EGFR mutation-positive female patients, as was AIS, MIA, and the lepidic-predominant subtype. The progression-free survival (PFS) of the EGFR mutation-positive patients was significantly better than that of the EGFR mutation-negative patients (75.8 vs 67.1%, p = 0.03). However, the multivariate analysis of clinicopathologic and histologic factors did not reveal the prognostic impact of the EGFR mutation status on PFS. The overall survival (OS) of the EGFR mutation-positive patients was significantly better than that of the EGFR mutation-negative patients (93.7 vs 63.4%, p < 0.01). However, in the multivariate analysis the EGFR mutation status was not significantly associated with OS.

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
Fig. 2

Similar content being viewed by others

References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.

    Article  PubMed  Google Scholar 

  2. Lemjabbar-Alaoui H, Hassan OU, Yang YW, Buchanan P. Lung cancer: biology and treatment options. Biochem Biophys Acta. 2015;1856:189–210.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Ettinger DS, Akerley W, Borghaei H, Chang AC, Cheney RT, Chirieac LR, et al. Non-small cell lung cancer, version 2.2013. J Nat Compr Cancer New. 2013;11:645–53.

    Article  Google Scholar 

  4. Travis W, Brambilla E, Noguchi M, Nicholson A, Geisinger K, Yatabe Y. International association for the study of lung cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6(2):244–85.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Hirscha FR, Scagliottib GV, Langerc CJ, Varella-Garciaa M, Franklina WA. Epidermal growth factor family of receptors in preneoplasia and lung cancer: perspectives for targeted therapies. Lung Cancer. 2003;41:S29–42.

    Article  Google Scholar 

  6. Kris MG, Natale RB, Herbst RS, Lynch TJ, Prager D, Belani CP, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancar. JAMA. 2003;290:2149–58.

    Article  CAS  PubMed  Google Scholar 

  7. Pérez-Soler R, Chachoua A, Hammond LA, Rowinsky EK, Huberman M, Karp D, et al. Determinants of tumor response and survival with erlotinib in patients with non–small-cell lung cancer. J Clin Oncol. 2004;22:3238–47.

    Article  PubMed  Google Scholar 

  8. Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, et al. Gefitinib or chemotherapy for non–small cell lung cancer with mutated EGFR. N Engl J Med. 2010;362:2380–8.

    Article  CAS  PubMed  Google Scholar 

  9. Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al. Gefitinib or carboplatin–paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947–57.

    Article  CAS  PubMed  Google Scholar 

  10. Shepherd FA, Pereira JR, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353:123–32.

    Article  CAS  PubMed  Google Scholar 

  11. 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;350:2129–39.

    Article  CAS  PubMed  Google Scholar 

  12. Mitsudomi T, Kosaka T, Yatabe Y. Biological and clinical implications of EGFR mutations in lung cancer. Int J Clin Oncol. 2006;11:190–8.

    Article  CAS  PubMed  Google Scholar 

  13. Yoshizawa A, Sumiyoshi S, Sonobe M, Kobayashi M, Fujimoto M, Kawakami F, et al. 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. 2013;8:52–61.

    Article  CAS  PubMed  Google Scholar 

  14. Villa C, Cagle PT, Johnson M, Patel JD, Yeldandi AV, Raj R, et al. Correlation of EGFR mutation status with predominant histologic subtype of adenocarcinoma according to the New Lung Adenocarcinoma Classification of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society. Arch Pathol Lab Med. 2014;138:1353–7.

    Article  PubMed  Google Scholar 

  15. Maturu VN, Singh N, Bal A, Gupta N, Das A, Behera D. Relationship of epidermal growth factor receptor activating mutations with histologic subtyping according to International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society 2011 adenocarcinoma classification and their impact on overall survival. Lung India. 2016;33:257–66.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Zhang Y, Sun Y, Pan Y, Li C, Shen L, Li Y, et al. Frequency of driver mutations in lung adenocarcinoma from female never-smokers varies with histological subtypes and age at diagnosis. Clin Cancer Res. 2012;18(7):1947–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Shim HS, Lee DH, Park EJ, Kim SH. Histopathologic characteristics of lung adenocarcinomas with epidermal growth factor receptor mutations in the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Lung Adenocarcinoma Classification. Arch Pathol Lab Med. 2011;135:1329–34.

    Article  PubMed  Google Scholar 

  18. Song Z, Zhu H, Guo Z, Wu W, Sun W, Zhang Y. Correlation of EGFR mutation and predominant histologic subtype according to the new lung adenocarcinoma classification in Chinese patients. Med Oncol. 2013;30:645.

    Article  PubMed  Google Scholar 

  19. Chen Z, Liu X, Zhao J, Yang H, Teng X. Correlation of EGFR mutation and histological subtype according to the IASLC/ATS/ERS classification of lung adenocarcinoma. Int J Clin Exp Pathol. 2014;7(11):8039–45.

    PubMed  PubMed Central  Google Scholar 

  20. Russell PA, Barnett SA, Walkiewicz M, Wainer Z, Conron M, Wright GM, et al. Correlation of mutation status and survival with predominant histologic subtype according to the New IASLC/ATS/ERS lung adenocarcinoma classification in Stage III (N2) patients. J Thorac Oncol. 2013;8:461–8.

    Article  PubMed  Google Scholar 

  21. Lu F, Li S, Dong B, Zhang S, Lv C, Yang Y. Identification of lung adenocarcinoma mutation status based on histologic subtype: Retrospective analysis of 269 patients. Thorac Cancer. 2016;7:17–23.

    Article  CAS  PubMed  Google Scholar 

  22. Sun Y, Yu X, Shi X, Hong W, Zhao J, Shi L. Correlation of survival and EGFR mutation with predominant histologic subtype according to the new lung adenocarcinoma classification in stage IB patients. World J Surg Oncol. 2014;12:148.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010;11:121–8.

    Article  CAS  PubMed  Google Scholar 

  24. Hirsch FR, Jänne PA, Eberhardt WE, Cappuzzo F, Thatcher N, Robert Pirker R, et al. Epidermal growth factor receptor inhibition in lung cancer: status 2012. J Thorac Oncol. 2013;8:373–84.

    Article  CAS  PubMed  Google Scholar 

  25. Shi Y, Au JSK, Thongprasert S, Srinivasan S, Tsai CM, Khoa MT, et al. 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. 2014;9:154–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Jackman DM, Yeap BY, Sequist LV, Lindeman N, Holmes AJ, Joshi VA, et al. Exon19 deletion mutations of epidermal growth factor receptor are associated with prolonged survival non-small cell lung cancer patients treated with gefitinib or erlotinib. Clin Cancer Res. 2006;12:3908–14.

    Article  CAS  PubMed  Google Scholar 

  27. Sasaki H, Shimizu S, Endo K, Takada M, Kawahara M, Tanaka H, et al. EGFR and erbB2 mutation status in japanese lung cancer patients. Int J Cancer. 2006;118:180–4.

    Article  CAS  PubMed  Google Scholar 

  28. Liu WS, Zhao LJ, Pang QS, Yuan ZY, Li B, Wang P. Prognostic value of epidermal growth factor receptor mutations in resected lung adenocarcinomas. Med Oncol. 2014;31:771.

    Article  PubMed  Google Scholar 

  29. Kobayashi N, Toyooka S, Ichimura K, Soh J, Yamamoto H, Matsuo K, et al. Non-BAC component but not epidermal growth factor receptor gene mutation is associated with poor outcomes in small adenocarcinoma of the lung. J Thorac Oncol. 2008;3:704–10.

    Article  PubMed  Google Scholar 

  30. Kosaka T, Yatabe Y, Endoh H, Kuwano H, Takahashi T, Mitsudomi T. Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Res. 2004;64:8919–23.

    Article  CAS  PubMed  Google Scholar 

  31. Lim KH, Huang MJ, Liu HC, Kuo HT, Tzen CY, Hsieh RK. Lack of prognostic value of EGFR mutations in primary resected non-small cell lung cancer. Med Oncol. 2007;24(4):388–93.

    Article  PubMed  Google Scholar 

  32. Nose N, Sugio K, Oyama T, Nozoe T, Uramoto H, Iwata T, et al. Association between estrogen receptor expression and epidermal growth factor receptor mutation in the postoperative prognosis of adenocarcinoma of the lung. J Clin Oncol. 2008;27:411–7.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Thoracic Surgery, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan

    Nozomu Motono, Aika Funasaki, Atsushi Sekimura, Katsuo Usuda & Hidetaka Uramoto

Authors
  1. Nozomu Motono
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aika Funasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Atsushi Sekimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Katsuo Usuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hidetaka Uramoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nozomu Motono.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

The study was approved by Ethics Committee of the Kanazawa Medical University in Japan.

Informed consent

All the study participants gave their written informed consent to participation in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Motono, N., Funasaki, A., Sekimura, A. et al. Prognostic value of epidermal growth factor receptor mutations and histologic subtypes with lung adenocarcinoma. Med Oncol 35, 22 (2018). https://doi.org/10.1007/s12032-018-1082-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-018-1082-y

Keywords

Search

Navigation