Comparison of Epidermal Growth Factor Receptor Mutations between Metastatic Lymph Node Diagnosed by EBUS-TBNA and Primary Tumor in Non-Small Cell Lung Cancer.
BACKGROUND
Although the use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is increasing for epidermal growth factor receptor (EGFR) testing in lung cancer, the discordance rate in EGFR mutations between lymph node (LN) samples obtained by EBUS-TBNA and primary tumor (PT) is not well known. Thus, we compared the EGFR mutation status of LN samples obtained by EBUS-TBNA and PTs to estimate the efficacy of using EBUS-TBNA specimens for EGFR testing in advanced, non-squamous, non-small cell lung cancer (NSCLC).


METHODS
Using data of patients from the EBUS-TBNA database (N = 1914) obtained between January 2009 and January 2013, we identified 100 treatment-naïve, advanced, non-squamous NSCLC patients (stage 3 and 4) with matched LN specimens obtained by EBUS-TBNA and PT specimens. Of these, 74 patients with paired specimens were feasible for EGFR mutation analysis, which we performed using a direct sequencing method.


RESULTS
Of the 74 cases, at least one major [exon 19 deleted (19del) and L858R] or minor (T790M, exon 20 insertion, and other point mutations) EGFR mutation was detected in 31 cases (41.9%), which included PT (n = 31, 41.9%) and LN (n = 28, 37.8%) specimens. Major mutations were detected in 25 PT (33.8%, 19del = 13, L858R = 12) and 22 LN (29.8%, 19del = 11, L858R = 11) specimens. The discordance rate in major mutations between matched PT and LN specimens was 4.1% (3/74). Among minor mutations, T790M was detected in LN specimen only in 2 cases with L858R in PT and LN. The discordance rate major and minor EGFR mutations combined between matched PT and LN specimens was 12% (9/74).


CONCLUSIONS
We observed a high concordance rate of major EGFR mutations between matched LN specimens sampled by EBUS-TBNA and PTs, suggesting that LN samples obtained by EBUS-TBNA from advanced non-squamous NSCLC patients are effective for use in EGFR mutation testing.
Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Hyo Jae
HJ
Kang
Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Bin
B
Hwangbo
Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Jin Soo
JS
Lee
Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Moon Soo
MS
Kim
Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Jong Mog
JM
Lee
Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.|Department of Pathology, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Geon-Kook
GK
Lee
Int J Oncol. 2001 May;18(5):1023-6
11295051
N Engl J Med. 2004 May 20;350(21):2129-39
15118073
Clin Cancer Res. 2006 Jan 1;12(1):43-8
16397022
Chest. 2007 Aug;132(2):597-602
17573511
Chest. 2008 Aug;134(2):368-374
18263688
Cancer Sci. 2008 May;99(5):929-35
18325048
J Thorac Oncol. 2009 Jul;4(7):809-15
19487967
Clin Cancer Res. 2009 Jul 15;15(14):4554-60
19584155
Eur Respir J. 2010 Feb;35(2):391-5
19643949
J Mol Diagn. 2010 Mar;12(2):257-64
20093389
N Engl J Med. 2010 Jun 24;362(25):2380-8
20573926
Ann Surg Oncol. 2011 Feb;18(2):543-50
20811949
J Thorac Oncol. 2010 Oct;5(10):1664-7
20871266
J Thorac Oncol. 2010 Oct;5(10):1706-13
20871269
Respirology. 2011 Jan;16(1):90-4
20920141
J Exp Clin Cancer Res. 2010 Oct 06;29:132
20925915
Int J Clin Oncol. 2011 Aug;16(4):335-44
21311943
Cancer Cytopathol. 2011 Apr 25;119(2):111-7
21400670
J Exp Clin Cancer Res. 2011 Mar 17;30:30
21414214
Chest. 2011 Nov;140(5):1319-1324
21527506
Clin Cancer Res. 2011 Jun 1;17(11):3812-21
21531810
J Clin Pathol. 2011 Nov;64(11):947-52
21725039
J Clin Oncol. 2011 Aug 1;29(22):2972-7
21730270
Lancet Oncol. 2011 Aug;12(8):735-42
21783417
Lung Cancer. 2012 Mar;75(3):321-5
21930325
Cancer Lett. 2012 Jan 1;314(1):63-72
21982684
J Thorac Oncol. 2012 Feb;7(2):355-64
22157369
J Thorac Dis. 2011 Mar;3(1):10-8
22263058
Am J Respir Crit Care Med. 2012 Jun 15;185(12):1316-22
22505743
J Clin Oncol. 2012 Sep 1;30(25):3077-83
22826274
J Clin Pathol. 2013 Feb;66(2):79-89
23172555
Target Oncol. 2013 Dec;8(4):237-42
23212424
Cancer Cytopathol. 2013 Jun;121(6):311-9
23225576
Chest. 2013 May;143(5 Suppl):e142S-e165S
23649436
Chest. 2013 May;143(5 Suppl):e211S-e250S
23649440
Ann Am Thorac Soc. 2013 Dec;10(6):636-43
24079724
J Exp Clin Cancer Res. 2014 Jan 08;33:5
24398248
J Thorac Oncol. 2014 Apr;9(4):506-11
24736073
Med Oncol. 2014 May;31(5):926
24748405
Asian Pac J Cancer Prev. 2014;15(11):4493-7
24969875
Respiration. 2014;88(6):500-17
25377908
QJM. 2016 Mar;109(3):167-73
26031706
J Clin Oncol. 2015 Oct 20;33(30):3488-515
26324367
Thorac Cancer. 2012 Nov;3(4):313-319
28920283
Thorac Cancer. 2012 Aug;3(3):262-268
28920306