Skip to main content

Advertisement

Log in

ARMS for EGFR mutation analysis of cytologic and corresponding lung adenocarcinoma histologic specimens

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Epidermal growth factor receptor (EGFR) mutation analysis is becoming a routine clinical practice for lung adenocarcinoma patients. Most patients with lung cancer are diagnosed at an advanced stage of the disease and are not suitable for surgical therapy. In many cases, cytologic specimens may be the only tissue available for diagnostic and molecular testing. Therefore, it is important to determine what condition the cytologic specimens should be in for adequately analyzing EGFR mutation status.

Methods

Fifty-eight paired cytologic and lung adenocarcinoma histologic specimens that satisfied 3 requisite parameters (>2 ng/μl DNA concentration, >30 tumor cells content, and >25 % tumor percentage) were collected. Exons 18 through 21 of the EGFR gene were analyzed by amplification refractory mutations system.

Results

The EGFR mutation concordance rate between cytologic specimens and corresponding histologic specimens was 100 %. A set of 30 paired specimens from different sites (lung and pleural fluids) from the same patient exhibited 100 % concordance in the EGFR mutation analysis results.

Conclusions

In this study, EGFR mutation presented a convenient and reliable method for the analysis of cytologic specimens that satisfied 3 requisite parameters (>2 ng/μl DNA concentration, >30 tumor cells content, and >25 % tumor percentage). We concluded that the specimens from both primary lung adenocarcinomas and metastatic lesions (such as pleural fluids) can be used for EGFR mutation analysis.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Aisner DL, Deshpande C, Baloch Z, Watt CD, Litzky LA, Malhotra B et al (2013) Evaluation of EGFR mutation status in cytology specimens: an institutional experience. Diagn Cytopathol 41:316–323

    Article  CAS  PubMed  Google Scholar 

  • Boyle P, Levin B (2008) World cancer report 2008. International Agency for Research on Cancer, Lyon

    Google Scholar 

  • Bruno P, Mariotta S, Ricci A, Duranti E, Scozzi D, Noto A et al (2011) Reliability of direct sequencing of EGFR: comparison between cytological and histological samples from the same patient. Anticancer Res 31:4207–4210

    CAS  PubMed  Google Scholar 

  • Chowdhuri SR, Xi L, Pham TH, Hanson J, Rodriguez-Canales J, Berman A et al (2012) EGFR and KRAS mutation analysis in cytologic samples of lung adenocarcinoma enabled by laser capture microdissection. Mod Pathol 25:548–555

    Article  CAS  PubMed  Google Scholar 

  • Curado MP, Edwards B, Shin HR, Storm H, Ferlay J, Heanue M et al (2007) Cancer incidence in five continents, vol IX. IARC Scientific Publications, Lyon

    Google Scholar 

  • D’Angelo SP, Park B, Azzoli CG, Kris MG, Rusch V, Ladanyi M et al (2011a) Reflex testing of resected stage I through III lung adenocarcinomas for EGFR and KRAS mutation: report on initial experience and clinical utility at a single center. J Thorac Cardiovasc Surg 141:476–480

    Article  PubMed  Google Scholar 

  • D’Angelo SP, Pietanza MC, Johnson ML, Riely GJ, Miller VA, Sima CS et al (2011b) Incidence of EGFR exon 19 deletions and L858R in tumor specimens from men and cigarette smokers with lung adenocarcinomas. J Clin Oncol 29:2066–2070

    Article  PubMed Central  PubMed  Google Scholar 

  • da Cunha Santos G, Saieg MA, Geddie W, Leighl N (2011) EGFR gene status in cytological samples of nonsmall cell lung carcinoma: controversies and opportunities. Cancer Cytopathol 119:80–91

    Article  CAS  Google Scholar 

  • Ellison G, Donald E, McWalter G, Knight L, Fletcher L, Sherwood J et al (2010) A comparison of ARMS and DNA sequencing for mutation analysis in clinical biopsy samples. J Exp Clin Cancer Res 29:132

    Article  PubMed Central  PubMed  Google Scholar 

  • Girard N, Sima CS, Jackman DM, Sequist LV, Chen H, Yang JC et al (2012) Nomogram to predict the presence of EGFR activating mutation in lung adenocarcinoma. Eur Respir J 39:366–372

    Article  CAS  PubMed  Google Scholar 

  • Gupta R, Dastane AM, Forozan F, Riley-Portuguez A, Chung F, Lopategui J et al (2009) Evaluation of EGFR abnormalities in patients with pulmonary adenocarcinoma: the need to test neoplasms with more than one method. Mod Pathol 22:128–133

    Article  CAS  PubMed  Google Scholar 

  • 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 12:380–386

    Article  CAS  PubMed  Google Scholar 

  • 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 99:923–929

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Khode R, Larsen DA, Culbreath BC, Parrish S, Walker KL, Sayage-Rabie L 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 121:361–369

    Article  CAS  PubMed  Google Scholar 

  • Kimura H, Kasahara K, Kawaishi M, Kunitoh H, Tamura T, Holloway B et al (2006) Detection of epidermal growth factor receptor mutations in serum as a predictor of the response to gefitinib in patients with non-small-cell lung cancer. Clin Cancer Res 12:3915–3921

    Article  CAS  PubMed  Google Scholar 

  • Ladanyi M, Pao W (2008) Lung adenocarcinoma: guiding EGFR-targeted therapy and beyond. Mod Pathol 21:S16–S22

    Article  CAS  PubMed  Google Scholar 

  • Malapelle U, de Rosa N, Rocco D, Bellevicine C, Crispino C, Illiano A et al (2012) EGFR and KRAS mutations detection on lung cancer liquid-based cytology: a pilot study. J Clin Pathol 65:87–91

    Article  PubMed  Google Scholar 

  • Navani N, Brown JM, Nankivell M, Woolhouse I, Harrison RN, Jeebun V et al (2012) Suitability of endobronchial ultrasound-guided transbronchial needle aspiration specimens for subtyping and genotyping of non-small cell lung cancer: a multicenter study of 774 patients. Am J Respir Crit Care Med 185:1316–1322

    Article  PubMed Central  PubMed  Google Scholar 

  • Pao W, Ladanyi M (2007) Epidermal growth factor receptor mutation testing in lung cancer: searching for the ideal method. Clin Cancer Res 13:4954–4955

    Article  CAS  PubMed  Google Scholar 

  • Reinersman JM, Johnson ML, Riely GJ, Chitale DA, Nicastri AD, Soff GA et al (2011) Frequency of EGFR and KRAS mutations in lung adenocarcinomas in African Americans. J Thorac Oncol 6:28–31

    Article  PubMed Central  PubMed  Google Scholar 

  • Savic S, Tapia C, Grilli B, Rufle A, Bihl MP, de Vito Barascud A et al (2008) Comprehensive epidermal growth factor receptor gene analysis from cytological specimens of non-small-cell lung cancers. Br J Cancer 98:154–160

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Shah PL, Singh S, Bower M, Livni N, Padley S, Nicholson AG (2006) The role of transbronchial fine needle aspiration in an integrated care pathway for the assessment of patients with suspected lung cancer. J Thorac Oncol 1:324–327

    Article  PubMed  Google Scholar 

  • Smouse JH, Cibas ES, Janne PA, Joshi VA, Zou KH, Lindeman NI (2009) EGFR mutations are detected comparably in cytologic and surgical pathology specimens of nonsmall cell lung cancer. Cancer 117:67–72

    PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sun PL, Jin Y, Kim H, Lee CT, Jheon S, Chung JH (2013) High concordance of EGFR mutation status between histologic and corresponding cytologic specimens of lung adenocarcinomas. Cancer Cytopathol 121:311–319

    Article  CAS  PubMed  Google Scholar 

  • Tanaka T, Nagai Y, Miyazawa H, Koyama N, Matsuoka S, Sutani A et al (2007) Reliability of the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp based test for epidermal growth factor receptor mutations integrated into the clinical practice for non-small cell lung cancers. Cancer Sci 98:246–252

    Article  CAS  PubMed  Google Scholar 

  • Yatabe Y, Matsuo K, Mitsudomi T (2011) Heterogeneous distribution of EGFR mutations is extremely rare in lung adenocarcinoma. J Clin Oncol 29:2972–2977

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank all of the patients who participated in this study.

Conflict of interest

The authors declare that there are no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jie Zhang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, J., Zhao, R., Zhang, J. et al. ARMS for EGFR mutation analysis of cytologic and corresponding lung adenocarcinoma histologic specimens. J Cancer Res Clin Oncol 141, 221–227 (2015). https://doi.org/10.1007/s00432-014-1807-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-014-1807-z

Keywords

Navigation