title: Immunohistochemistry reliably detects ALK rearrangements in patients with advanced non-small-cell lung cancer.
abstract: Accurate determination of anaplastic lymphoma kinase (ALK) rearrangements is critical in identifying ALK-positive patients for targeted therapy in non-small-cell lung cancer (NSCLC). Fluorescence in situ hybridization (FISH) is the current standard method to detect ALK rearrangements but is technically challenging and costly. We compared optimised immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization techniques in this study of 139 samples of advanced NSCLC with non-squamous histology. ALK alteration was found in 32.6 % (43/132) of patients by FISH, 32.9 % (45/137) of patients by IHC and 27.9 % (34/122) of samples by qRT-PCR (concordance rate of 96.9 % between FISH and IHC, 95.7 % between FISH and qRT-PCR, P < 0.001). IHC sensitivity and specificity were 97.7 % and 96.6 %, respectively, while the sensitivity and specificity of qRT-PCR were 89.2 % and 98.7 %, respectively. ALK rearrangements were more common in young patients (P = 0.007), non-smokers or light smokers (P = 0.008) and adenocarcinoma histology, especially with signet ring cell features (P < 0.001). Optimised IHC could be a useful method in screening ALK rearrangements in clinical practice with qRT-PCR as an alternative diagnostic tool to clarify specific ALK variants.
authors: Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.
authors: Xiao-Hong
authors: XH
authors: Han
authors: Ning-Ning
authors: NN
authors: Zhang
authors: Li
authors: L
authors: Ma
authors: Dong-Mei
authors: DM
authors: Lin
authors: Xue-Zhi
authors: XZ
authors: Hao
authors: Yu-Tao
authors: YT
authors: Liu
authors: Lin
authors: L
authors: Wang
authors: Peng
authors: P
authors: Liu
authors: Zheng
authors: Z
authors: Yuan
authors: Dan
authors: D
authors: Li
authors: Hua
authors: H
authors: Lin
authors: Yan
authors: Y
authors: Sun
authors: Yuan-Kai
authors: YK
authors: Shi
mesh_terms: D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
references: Clin Cancer Res. 2010 Mar 1;16(5):1561-71
references: 20179225
references: Lung Cancer. 2012 Jun;76(3):309-15
references: 22153831
references: Clin Cancer Res. 2012 Sep 1;18(17):4682-90
references: 22912387
references: Lung Cancer. 2011 Feb;71(2):241-3
references: 21168933
references: J Clin Oncol. 2009 Sep 10;27(26):4247-53
references: 19667264
references: Am J Pathol. 2009 Feb;174(2):661-70
references: 19147828
references: Respirology. 2013 Feb;18(2):233-7
references: 22957484
references: Lung Cancer. 2012 Aug;77(2):288-92
references: 22465695
references: J Thorac Oncol. 2011 May;6(5):905-12
references: 21358343
references: N Engl J Med. 2011 Feb 24;364(8):776-7; author reply 778
references: 21345113
references: J Thorac Oncol. 2011 Mar;6(3):459-65
references: 21278610
references: PLoS One. 2013 May 31;8(5):e64821
references: 23741400
references: Clin Cancer Res. 2012 Jul 15;18(14):3737-42
references: 22547770
references: J Thorac Oncol. 2012 Feb;7(2):348-54
references: 22071784
references: J Natl Compr Canc Netw. 2011 Dec;9(12):1328-30
references: 22157552
references: J Pharmacol Exp Ther. 2005 Dec;315(3):971-9
references: 16002463
references: J Thorac Oncol. 2012 Jan;7(1):98-104
references: 22124476
references: J Thorac Oncol. 2010 Dec;5(12):2039-40
references: 21102267
references: Zhongguo Fei Ai Za Zhi. 2012 Feb;15(2):112-6
references: 22336240
references: Curr Opin Investig Drugs. 2010 Dec;11(12):1477-90
references: 21154129
references: J Clin Oncol. 2006 May 10;24(14):2137-50
references: 16682732
references: Hum Pathol. 2009 Aug;40(8):1152-8
references: 19386350
references: Cancer Res. 2008 Jul 1;68(13):4971-6
references: 18593892
references: Nature. 2007 Aug 2;448(7153):561-6
references: 17625570
references: Clin Cancer Res. 2009 Aug 15;15(16):5216-23
references: 19671850
references: Mol Cancer. 2010 Jul 13;9:188
references: 20624322
references: J Thorac Oncol. 2011 Feb;6(2):244-85
references: 21252716
references: Clin Cancer Res. 2011 Dec 1;17(23):7213-8
references: 22010214
references: Clin Cancer Res. 2010 Nov 15;16(22):5581-90
references: 21062932
references: Indian J Surg Oncol. 2011 Sep;2(3):178-88
references: 22942608
references: Oncology. 2012;83(5):248-56
references: 22964709
references: Mod Pathol. 2009 Apr;22(4):508-15
references: 19234440
references: Clin Cancer Res. 2012 Oct 15;18(20):5682-9
references: 22908099
references: Arch Pathol Lab Med. 2012 Jul;136(7):796-803
references: 22742552