Detection of EGFR and KRAS gene mutations using suspension liquid-based cytology specimens in metastatic lung adenocarcinoma

Huan Zhao, Tian Qiu, Huiqin Guo, Jianming Ying, Junling Li, Zhihui Zhang, Huan Zhao, Tian Qiu, Huiqin Guo, Jianming Ying, Junling Li, Zhihui Zhang

Abstract

Background: The detection of EGFR and KRAS mutations of metastatic lung adenocarcinoma using liquid-based cytology suspension routine specimens from fine-needle aspiration remains controversial.

Results: The DNA of all specimens was extracted and real time PCR was performed successfully. The rate of EGFR and KARS mutations was 37.7% (58/154) and 5.8% (9/154), respectively. EGFR mutation rate was significantly higher in females than that in males (47.8% vs. 29.4%, P = 0.019). There were no significant differences among different age groups or different tumor sites. These results of EGFR and KRAS mutations using LBC specimens were consistant with the tissue samples. In 30 patients treated with tyrosine kinase inhibitors, complete response, partial response, stable disease and progress disease was observed in 2, 10, 13 and 5 patients, respectively.

Conclusions: Liquid-based cytology specimen is reliable and can be an alternative source for the detection of EGFR and KRAS mutations.

Methods: 154 fine-needle aspiration cytologic samples were obtained from patients with metastatic lung adenocarcinoma. The specimens included 21 cases of mediastinal lymph node 123 cases of neck nodules and 10 cases of subcutaneous nodules. After the diagnosis and count of tumor cells performed by cytopathologists, liquid-based cytology specimens with sufficient tumor cells were used for EGFR and KRAS testing using real-time PCR.

Keywords: EGFR; KRAS; adenocarcinoma; fine-needle aspiration; lung cancer.

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare that there are no competing interests.

Figures

Figure 1. Detection of EGFR and KRAS…
Figure 1. Detection of EGFR and KRAS mutations using suspension liquid-based cytology specimens from fine-needle aspiration in metastatic lung adenocarcinoma by real-time PCR
Representative images of positive (A, C) and negative (B, D) for EGFR and KRAS mutations by real-time PCR. Positive curve were indicated by red arrows.

References

    1. Eberhard DA, Johnson BE, Amler LC, Goddard AD, Heldens SL, Herbst RS. Mutationss in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol. 2005;23:5900–5909.
    1. Reck M, Popat S, Reinmuth N, De Ruysscher D, Kerr KM, Peters S. ESMO Guidelines Working Group. Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25:iii27–39.
    1. Stigt JA, ‘tHart NA, Knol AJ, Uil SM, Groen HJ. Pyrosequencing analysis of EGFR and KRAS mutationss in EUS and EBUS-derived cytologic samples of adenocarcinomas of the lung. J Thorac Oncol. 2013;8:1012–1018.
    1. Bellevicine C, Malapelle U, Vigliar E, de Luca C, Troncone G. Epidermal growth factor receptor test performed on liquid-based cytology lung samples, experience of an academic referral center. Acta Cytol. 2014;58:589–594.
    1. Lozano MD, Labiano T, Echeveste J, Gurpide A, Martín-Algarra S, Zhang G. Assessment of EGFR and KRAS mutations status from FNAs and core-needle biopsies of non-small cell lung cancer. Cancer Cytopathol. 2015;123:230–236.
    1. Krawczyk P, Ramlau R, Chorostowska-Wynimko J, Powrózek T, Lewandowska MA, Limon J, Wasąg B. The efficacy of EGFR gene mutations testing in various samples from non-small cell lung cancer patients: a multicenter retrospective study. J Cancer Res Clin Oncol. 2015;141:61–68.
    1. Veldore VH, Rao RM, Kakara S, Pattanayak S, Tejaswi R, Sahoo R. Epidermal growth factor receptor mutations in non-small-cell lung carcinomas: a retrospective analysis of 1036 lung cancer specimens from a network of tertiary cancer care centers in India. Indian J Cancer. 2013;50:87–93.
    1. Malapelle U, de Rosa N, Rocco D, Bellevicine C, Crispino C, Illiano A. EGFR and KRAS mutationss detection on lung cancer liquid-based cytology: a pilot study. J Clin Pathol. 2012;65:87–91.
    1. Billah S, Stewart J, Staerkel G, Chen S, Gong Y, Guo M. EGFR and KRAS mutationss in lung carcinoma: molecular testing by using cytology specimens. Cancer Cytopathol. 2011;119:111–117.
    1. Lindeman NI, Cagle PT, Beasley MB, Chitale DA, Dacic S, Giaccone G, Jenkins RB, Kwiatkowski DJ, Saldivar JS, Squire J, Thunnissen E, Ladanyi M, College of American Pathologists International Association for the Study of Lung Cancer and Association for Molecular Pathology 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 Mol Diagn. 2013;15:415–453.
    1. Aisner DL, Marshall CB. Molecular pathology of non-small cell lung cancer: a practical guide. Am J Clin Pathol. 2012;138:332–346.
    1. Dejmek A, Zendehrokh N, Tomaszewska M, Edsjö A. Preparation of DNA from cytological material: effects of fixation, staining, and mounting medium on DNA yield and quality. Cancer Cytopathol. 2013;121:344–353.
    1. Zhao H, Zhang ZH, Zhou B, Xiao T, Pan QJ, Guo HQ. Detection of BRAF c.1799T > A (p.V600E) mutation using residual routine fine-needle aspiration specimens of papillary thyroid carcinoma. Diagn Cytopathol. 2015;43:786–790.
    1. Rossi ED, Martini M, Capodimonti S, Lombardi CP, Pontecorvi A, Vellone VG. BRAF (V600E) mutations analysis on liquid-based cytology-processed aspiration biopsies predicts bilaterality and lymph node involvement in papillary thyroid microcarcinoma. Cancer Cytopathol. 2013;121:291–297.
    1. Aisner DL, Sams SB. The role of cytology specimens in molecular testing of solid tumors: techniques, limitations, and opportunities. Diagn Cytopathol. 2012;40:511–524.
    1. Son C, Kang EJ, Roh MS. Strategic management of transthoracic needle aspirates for histological subtyping and EGFR testing in patients with peripheral lung cancer: An institutional experience. Diagn Cytopathol. 2015;43:532–538.
    1. Araya T, Demura Y, Kasahara K, Matsuoka H, Yamamura K, Nishitsuji M. Usefulness of transesophageal bronchoscopic ultrasound-guided fine-needle aspiration in the pathologic and molecular diagnosis of lung cancer lesions adjacent to the esophagus. J Bronchology Interv Pulmonol. 2013;20:121–126.
    1. Wu CY, Hou LK, Ren SX, Su B, Chen G. High feasibility of liquid-based cytological samples for detection of EGFR mutationss in Chinese patients with NSCLC. Asian Pac J Cancer Prev. 2014;15:7885–7889.
    1. Dearden S, Stevens J, Wu YL, Blowers D. Mutation incidence and coincidence in non small-cell lung cancer: meta-analyses by ethnicity and histology (mutMap) Ann Oncol. 2013;24:2371–2376.
    1. Yatabe Y, Kerr KM, Utomo A, Rajadurai P, Tran VK, Du X. EGFR mutations testing practices within the Asia Pacific region: results of a multicenter diagnostic survey. J Thorac Oncol. 2015;10:438–445.
    1. Gahr S, Stoehr R, Geissinger E, Ficker JH, Brueckl WM, Gschwendtner A. EGFR mutationsal status in a large series of Caucasian European NSCLC patients: data from daily practice. Br J Cancer. 2013;109:1821–1828.
    1. Er TK, Lin CW, Liu TC, Chen CC, Wang LH, Hsieh LL. Increase EGFR Mutationss Detection Rate in Lung Adenocarcinoma by Real-Time PCR Screening Followed by Direct Sequencing. Appl Immunohistochem Mol Morphol. 2015;23:343–348.
    1. Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362:2380–2388.
    1. Yoshida K, Yatabe Y, Park JY, Shimizu J, Horio Y, Matsuo K. Prospective validation for prediction of gefitinib sensitivity by epidermal growth factor receptor gene mutations in patients with non-small cell lung cancer. J Thorac Oncol. 2007;2:22–28.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다