High Feasibility of Liquid-Based Cytological Samples for Detection of EGFR Mutations in Chinese Patients with NSCLC

  • Wu, Chun-Yan (Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine) ;
  • Hou, Li-Kun (Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine) ;
  • Ren, Sheng-Xiang (Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine) ;
  • Su, Bo (Laboratory, Shanghai Pulmonary Hospital Affiliated with Tongji University, Tongji University School of Medicine) ;
  • Chen, Gang (Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine)
  • Published : 2014.10.11


Background: Activating mutations of epidermal growth factor receptor (EGFR) could predict response to tyrosine kinase inhibitor (TKI) treatment in patients with non-small cell lung cancer (NSCLC). However, the detection of EGFR mutation is frequently challenging in clinical practice for the lack of tumor tissue. The aim of this study was to investigate the feasibility of performing EGFR mutation testing on various types of liquid-based cytology (LBC) samples. Materials and Methods: A total of 434 liquid-based cytology samples were collected from March 2010 and November 2013. Among them, 101 with diagnosis of lung adenocarcinoma had paired surgically resected specimens. The ADx Amplification Refractory Mutation System (ADx-ARMS) was used to determine EGFR mutation status both in LBC and resected samples. Results: All liquid-based cytology samples were adequate for EGFR mutation analysis. The mutation rate was 50.5% in the 434 NSCLC patients with LBC samples and the incidence rates of EGFR mutation were consistent among different specimens. We also detected EGFR positives in 52.5% (53/101) patients with paired histologic specimens. The concordance rate of EGFR mutation between LBC samples and paired histologic specimens was 92.1%. Conclusions: Our results suggest that liquid-based cytology samples are highly reliable for EGFR mutation testing in patients with NSCLC.


  1. Chu H, Zhong C, Xue G, et al (2013). Direct sequencing and amplification refractory mutation system for epidermal growth factor receptor mutations in patients with non-small cell lung cancer. Oncol Rep, 30, 2311-5.
  2. Alimujiang S, Zhang T, Han ZhG, et al (2013). Epidermal growth factor receptor tyrosine kinase inhibitor versus placebo as maintenance therapy for advanced nonsmall-cell lung cancer: a meta-analysis of randomized controlled trials. Asian Pac J Cancer Prev, 14, 2413-9.
  3. Aisner DL, Deshpande C, Baloch Z, et al (2013). Evaluation of EGFR mutation status in cytology specimens: an institutional experience. Diagn Cytopathol, 41, 316-23.
  4. Chen G, Feng J, Zhou C, et al (2013). Quality of life (QoL) analyses from OPTIMAL (CTONG-0802), a phase III, randomised, open-label study of first-line erlotinib versus chemotherapy in patients with advanced EGFR mutationpositive non-small-cell lung cancer (NSCLC). Ann Oncol, 24, 1615-22.
  5. Dejmek A, Zendehrokh N, Tomaszewska M, Edsjo A (2013). Preparation of DNA from cytological material: effects of fixation, staining, and mounting medium on DNA yield and quality. Cancer Cytopathol, 121, 344-53.
  6. Ellison G, Donald E, McWalter G, et al (2010). A comparison of ARMS and DNA sequencing for mutation analysis in clinical biopsy samples (serial online). J Exp Clin Cancer Res, 29, 132.
  7. Hansen T, Pedersen H, Brauner V, Hariri J (2011). Control specimens for immunocytochemistry in liquid-based cytology. Cytopathology, 22, 243-6.
  8. Han HS, Eom DW, Kim JH, et al (2011). EGFR mutation status in primary lung adenocarcinomas and corresponding metastatic lesions: discordance in pleural metastases. Clin Lung Cancer, 12, 380-6.
  9. Jing CHW, Wang ZH, Cao XH, Ma R, Wu JZh (2013) High resolution melting analysis for epidermal growth factor receptor mutations in formalin-fixed paraffin-embedded tissue and plasma free DNA from non-small cell lung cancer patients. Asian Pac J Cancer Prev, 14, 6619-23
  10. Han JY, Park K, Kim SW, et al (2012). First-SIGNAL: first-line single-agent iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung. J Clin Oncol, 30, 1122-8.
  11. Inoue A, Kobayashi K, Maemondo M, et al (2013). Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for chemonaïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002). Ann Oncol, 24, 54-9.
  12. Jia XL, Chen G (2011). EGFR and KRAS mutations in Chinese patients with adenosquamous carcinoma of the lung. Lung Cancer, 74, 396-400.
  13. Khode R, Larsen DA, Culbreath BC, et al (2013). Comparative study of epidermal growth factor receptor mutation analysis on cytology smears and surgical pathology specimens from primary and metastatic lung carcinomas. Cancer Cytopathol, 121, 361-9.
  14. 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.
  15. Ladanyi M, Pao W (2008). Lung adenocarcinoma: guiding EGFR-targeted therapy and beyond. Mod Pathol, 21, 16-22.
  16. Malapelle U, de Rosa N, Rocco D, et al (2012). EGFR and KRAS mutations detection on lung cancer liquid-based cytology: a pilot study. J Clin Pathol, 65, 87-91.
  17. Pao W, Ladanyi M (2007). Epidermal growth factor receptor mutation testing in lung cancer: searching for the ideal method. Clin Cancer Res, 13, 4954-5.
  18. Sun PL, Jin Y, Kim H, et al (2013). High concordance of EGFR mutation status between histologic and corresponding cytologic specimens of lung adenocarcinomas. Cancer Cytopathol, 121, 311-9.
  19. Pang B, Dettmer M, Ong CW, et al (2012). The positive impact of cytological specimens for EGFR mutation testing in nonsmall cell lung cancer: a single South East Asian laboratory's analysis of 670 cases. Cytopathology, 23, 229-36.
  20. Rich JN, Rasheed BK, Yan H (2004). EGFR mutations and sensitivity to gefitinib. N Engl J Med, 351, 1260-1.
  21. Sholl LM, Xiao Y, Joshi V, et al (2010). EGFR mutation is a better predictor of response to tyrosine kinase inhibitors in non-small cell lung carcinoma than FISH, CISH, and immunohistochemistry. Am J Clin Pathol, 133, 922-34.
  22. Wallace WA, Monaghan HM, Salter DM, Gibbons MA, Skwarski KM (2007). Endobronchial ultrasound-guided fine-needle aspiration and liquid-based thin-layer cytology. J Clin Pathol, 60, 388-91.
  23. Wu GP, Wang EH, Li JH, Fu ZM, Han S (2009). Clinical application of the liquid-based cytological test in cytological screening of sputum for the diagnosis of lung cancer. Respirology, 14, 124-8
  24. Wu YL, Zhou C, Hu CP, et al (2014). Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol, 15, 213-22.
  25. Wang F, Fang P, Hou DY, Leng ZJ, Cao LJ (2014). Comparison of epidermal growth factor receptor mutations between primary tumors and lymph nodes in non-small cell lung cancer: a review and meta-analysis of published data. Asian Pac J Cancer Prev, 15, 4493-7.
  26. Yatabe Y, Matsuo K, Mitsudomi T (2011). Heterogeneous distribution of EGFR mutations is extremely rare in lung adenocarcinoma. J Clin Oncol, 29, 2972-7.

Cited by

  1. Preanalytic parameters in epidermal growth factor receptor mutation testing for non-small cell lung carcinoma: A review of cytologic series vol.123, pp.11, 2015,
  2. Biomarker Testing in Lung Carcinoma Cytology Specimens: A Perspective From Members of the Pulmonary Pathology Society vol.140, pp.11, 2016,
  3. Preanalytic specimen triage: Smears, cell blocks, cytospin preparations, transport media, and cytobanking vol.125, pp.S6, 2017,
  4. To Obtain More With Less: Cytologic Samples With Ancillary Molecular Techniques—The Useful Role of Liquid-Based Cytology vol.142, pp.3, 2018,