Analysis of Epidermal Growth Factor Receptor (EGFR) Gene Mutations in Pathologically Confirmed Lung Adenocarcinoma by Endobronchial Ultrasound-guided Transbronchial Needle Aspiration_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

CHENSu-feng ^1,2 , ZHANGYa-wei ^1,2 , HUHong ^1,2 , ZHANGJie ^1,2 , SUNYi-hua ^1,2 , WANGLong-fu ^2,3 , CHENYing ^2,3 , WANGYan-li ^2,3 , XIANGJia-qing ^1,2 ,  CHENHai-quan ^1,2

1. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center;
2. Department of Oncology, Shanghai Medical College, Fudan University, shanghai 200032, P. R. China;
3. Department of Pathology, Fudan University Shanghai Cancer Center, shanghai 200032, P. R. China;

Corresponding?author：

CHENHai-quan, Email: hqchen1@yahoo.com

Keywords：

Lung neoplasm; Endobronchial ultrasonography; Transbronchial needle aspiration; Gene; Mutation

DOI：

10.7507/1007-4848.20150013

Video：

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Objective To analyse epidermal growth factor receptor (EGFR) gene mutations in pathologically confirmed lung adenocarcinoma (LAC) samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Methods Clinical data of 964 consecutive patients who underwent EBUS-TBNA in Department of Thoracic Surgery, Fudan University Shanghai Cancer Center from April 2009 to September 2013 were retrospectively reviewed. EGFR gene mutations in 77 LAC patients who were comfirmed by cell morphology and immunohistochemistry were analyzed. There were 48 males and 29 females with their median age of 61 (range 33-78) years, and 43 patients were smokers. Results All the 77 LAC patients were confirmed by immunohistochemistry. Among them, 31 patients (40.26%) were found to have EGFR gene mutations. There was no statistical difference in EGFR gene mutations between male and female patients (P=0.088). Mutation rate of EGFR genes of non-smokers was significantly higher than that of smokers (P=0.032). Conclusion Samples obtained by EBUS-TBNA can be used for EGFR gene mutations analysis. The mutation rate of EGFR genes of non-smokers is higher than that of smokers.

Citation： CHENSu-feng, ZHANGYa-wei, HUHong, ZHANGJie, SUNYi-hua, WANGLong-fu, CHENYing, WANGYan-li, XIANGJia-qing, CHENHai-quan. Analysis of Epidermal Growth Factor Receptor (EGFR) Gene Mutations in Pathologically Confirmed Lung Adenocarcinoma by Endobronchial Ultrasound-guided Transbronchial Needle Aspiration. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2015, 22(1): 44-47. doi: 10.7507/1007-4848.20150013 Copy

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2.	Shih JY, Gow CH, Yu CJ, et al. Epidermal growth factor receptor mutations in needle biopsy/aspiration samples predict response to gefitinib therapy and survival of patients with advanced nonsmall cell lung cancer. Int J Cancer, 2006, 118(4):963-969.
3.	Horiike A, Kimura H, Nishio K, et al. Detection of epidermal growth factor receptor mutation in transbronchial needle aspirates of non-small cell lung cancer. Chest, 2007, 131(6):1628-1634.
4.	陳蘇峰, 胡鴻, 張杰, 等. 單中心500 例支氣管內超聲引導針吸活檢術分析. 中華胸心血管外科雜志, 2012, 28(8):494-495.
5.	Fukuoka M, Yano S, Giaccone G, et al. Multi-institutional randomized phase Ⅱ trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial)[corrected]. J Clin Oncol, 2003, 21(12):2237-2246.
6.	Kris MG, Natale RB, Herbst RS, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer:a randomized trial. JAMA, 2003, 290(16):2149-2158.
7.	Lynch TJ, Bell DW, Sordella R, 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(21):2129-2139.
8.	Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer:correlation with clinical response to gefitinib therapy. Science, 2004, 304(5676):1497-1500.
9.	Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med, 2005, 353(2):123-132.
10.	Krawczyk P, Kowalski DM, Krawczyk KW, et al. Predictive and prognostic factors in second- and third-line erlotinib treatment in NSCLC patients with known status of the EGFR gene. Oncol Rep, 2013, 30(3):1463-1472.
11.	Wu YL, Zhou C, Hu CP, et al. 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, 2014, 15(2):213-222.
12.	Travis WD, Brambilla E, Noguchi M, et al. 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):244-285.
13.	Schmid-Bindert G, Wang Y, Jiang H, et al. EBUS-TBNA provides highest RNA yield for multiple biomarker testing from routinely obtained small biopsies in non-small cell lung cancer patients-a comparative study of three different minimal invasive sampling methods. PLoS One, 2013, 8(10):e77948.
14.	Folch E, Yamaguchi N, VanderLaan PA, et al. Adequacy of lymph node transbronchial needle aspirates using convex probe endobronchial ultrasound for multiple tumor genotyping techniques in non-small-cell lung cancer. J Thorac Oncol, 2013, 8(11):1438-1444.
15.	Reynolds JP, Tubbs RR, Minca EC, et al. EGFR mutational genotyping of liquid based cytology samples obtained via fine needle aspiration (FNA) at endobronchial ultrasound of non-small cell lung cancer (NSCLC). Lung Cancer, 2014, Sep 22[Epub ahead of print].
16.	趙輝, 王俊, 李劍鋒, 等. 支氣管內超聲引導針吸活檢術在胸部疾病中的臨床應用價值. 中國胸心血管外科臨床雜志, 2010, 17(5):353-356.
17.	Kosaka T, Yatabe Y, Endoh H, et al. Mutations of the epidermal growth factor receptor gene in lung cancer:biological and clinical implications. Cancer Res, 2004, 64(24):8919-8923.
18.	Shigematsu H, Lin L, Takahashi T, et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst, 2005, 97(5):339-346.
19.	Travis WD, Travis LB, Devesa SS. Lung cancer. Cancer, 1995, 75(1 Suppl):191-202.
20.	Huang SF, Liu HP, Li LH, et al. High frequency of epidermal growth factor receptor mutations with complex patterns in nonsmall cell lung cancers related to gefitinib responsiveness in Taiwan. Clin Cancer Res, 2004, 10(24):8195-8203.
21.	Sonobe M, Manabe T, Wada H, et al. Mutations in the epidermal growth factor receptor gene are linked to smoking-independent, lung adenocarcinoma. Br J Cancer, 2005, 93(3):355-363.
22.	Sugio K, Uramoto H, Ono K, et al. Mutations within the tyrosine kinase domain of EGFR gene specifically occur in lung adenocarcinoma patients with a low exposure of tobacco smoking. Br J Cancer, 2006, 94(6):896-903.
23.	張新勇, 徐麗艷, 汪惠, 等. EGFR 基因突變與酪氨酸激酶抑制劑療效及預后之間的關系. 中國肺癌雜志, 2008, 11(2):206-213.
24.	陳穎, 平波, 王龍富, 等. 細胞病理學在經支氣管鏡超聲引導針吸活檢術中的作用. 中華病理學雜志, 2012, 41(1):44-47.
25.	Gazdar AF, Shigematsu H, Herz J, et al. Mutations and addiction to EGFR:the Achilles ‘heal’ of lung cancers? Trends Mol Med, 2004, 10(10):481-486.
26.	Thu KL, Vucic EA, Chari R, et al. Lung adenocarcinoma of never smokers and smokers harbor differential regions of genetic alteration and exhibit different levels of genomic instability. PLoS One, 2012, 7(3):e33003.

1. ?Kimura H, Fujiwara Y, Sone T, et al. EGFR mutation status in tumour-derived DNA from pleural effusion fluid is a practical basis for predicting the response to gefitinib. Br J Cancer, 2006, 95(10):1390-1395.
2. Shih JY, Gow CH, Yu CJ, et al. Epidermal growth factor receptor mutations in needle biopsy/aspiration samples predict response to gefitinib therapy and survival of patients with advanced nonsmall cell lung cancer. Int J Cancer, 2006, 118(4):963-969.
3. Horiike A, Kimura H, Nishio K, et al. Detection of epidermal growth factor receptor mutation in transbronchial needle aspirates of non-small cell lung cancer. Chest, 2007, 131(6):1628-1634.
4. 陳蘇峰, 胡鴻, 張杰, 等. 單中心500 例支氣管內超聲引導針吸活檢術分析. 中華胸心血管外科雜志, 2012, 28(8):494-495.
5. Fukuoka M, Yano S, Giaccone G, et al. Multi-institutional randomized phase Ⅱ trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial)[corrected]. J Clin Oncol, 2003, 21(12):2237-2246.
6. Kris MG, Natale RB, Herbst RS, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer:a randomized trial. JAMA, 2003, 290(16):2149-2158.
7. Lynch TJ, Bell DW, Sordella R, 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(21):2129-2139.
8. Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer:correlation with clinical response to gefitinib therapy. Science, 2004, 304(5676):1497-1500.
9. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med, 2005, 353(2):123-132.
10. Krawczyk P, Kowalski DM, Krawczyk KW, et al. Predictive and prognostic factors in second- and third-line erlotinib treatment in NSCLC patients with known status of the EGFR gene. Oncol Rep, 2013, 30(3):1463-1472.
11. Wu YL, Zhou C, Hu CP, et al. 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, 2014, 15(2):213-222.
12. Travis WD, Brambilla E, Noguchi M, et al. 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):244-285.
13. Schmid-Bindert G, Wang Y, Jiang H, et al. EBUS-TBNA provides highest RNA yield for multiple biomarker testing from routinely obtained small biopsies in non-small cell lung cancer patients-a comparative study of three different minimal invasive sampling methods. PLoS One, 2013, 8(10):e77948.
14. Folch E, Yamaguchi N, VanderLaan PA, et al. Adequacy of lymph node transbronchial needle aspirates using convex probe endobronchial ultrasound for multiple tumor genotyping techniques in non-small-cell lung cancer. J Thorac Oncol, 2013, 8(11):1438-1444.
15. Reynolds JP, Tubbs RR, Minca EC, et al. EGFR mutational genotyping of liquid based cytology samples obtained via fine needle aspiration (FNA) at endobronchial ultrasound of non-small cell lung cancer (NSCLC). Lung Cancer, 2014, Sep 22[Epub ahead of print].
16. 趙輝, 王俊, 李劍鋒, 等. 支氣管內超聲引導針吸活檢術在胸部疾病中的臨床應用價值. 中國胸心血管外科臨床雜志, 2010, 17(5):353-356.
17. Kosaka T, Yatabe Y, Endoh H, et al. Mutations of the epidermal growth factor receptor gene in lung cancer:biological and clinical implications. Cancer Res, 2004, 64(24):8919-8923.
18. Shigematsu H, Lin L, Takahashi T, et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst, 2005, 97(5):339-346.
19. Travis WD, Travis LB, Devesa SS. Lung cancer. Cancer, 1995, 75(1 Suppl):191-202.
20. Huang SF, Liu HP, Li LH, et al. High frequency of epidermal growth factor receptor mutations with complex patterns in nonsmall cell lung cancers related to gefitinib responsiveness in Taiwan. Clin Cancer Res, 2004, 10(24):8195-8203.
21. Sonobe M, Manabe T, Wada H, et al. Mutations in the epidermal growth factor receptor gene are linked to smoking-independent, lung adenocarcinoma. Br J Cancer, 2005, 93(3):355-363.
22. Sugio K, Uramoto H, Ono K, et al. Mutations within the tyrosine kinase domain of EGFR gene specifically occur in lung adenocarcinoma patients with a low exposure of tobacco smoking. Br J Cancer, 2006, 94(6):896-903.
23. 張新勇, 徐麗艷, 汪惠, 等. EGFR 基因突變與酪氨酸激酶抑制劑療效及預后之間的關系. 中國肺癌雜志, 2008, 11(2):206-213.
24. 陳穎, 平波, 王龍富, 等. 細胞病理學在經支氣管鏡超聲引導針吸活檢術中的作用. 中華病理學雜志, 2012, 41(1):44-47.
25. Gazdar AF, Shigematsu H, Herz J, et al. Mutations and addiction to EGFR:the Achilles ‘heal’ of lung cancers? Trends Mol Med, 2004, 10(10):481-486.
26. Thu KL, Vucic EA, Chari R, et al. Lung adenocarcinoma of never smokers and smokers harbor differential regions of genetic alteration and exhibit different levels of genomic instability. PLoS One, 2012, 7(3):e33003.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Analysis of Epidermal Growth Factor Receptor (EGFR) Gene Mutations in Pathologically Confirmed Lung Adenocarcinoma by Endobronchial Ultrasound-guided Transbronchial Needle Aspiration

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