title: Expression of the CXCR4 ligand SDF-1/CXCL12 is prognostically important for adenocarcinoma and large cell carcinoma of the lung.
abstract: The SDF-1/CXCR4 axis is associated with tumor progression and has been reported as a prognostic parameter, although with conflicting data for non-small cell lung cancer (NSCLC). This study examines a large cohort of clinically and pathologically well-characterized NSCLC patients and includes the activated form of CXCR4 (pCXCR4), which has not been studied in this context so far. SDF-1, CXCR4, and pCXCR4 were assessed immunohistochemically in 371 surgically resected NSCLC using a standardized tissue microarray platform. Extensive clinical and pathological data and a postoperative follow-up period of 17 years enabled detailed correlations. CXCR4 and pCXCR4 were frequently expressed on squamous cell carcinoma. Membranous expression of SDF-1 was a marker of poor prognosis and proved to be an independent prognostic parameter for the entire cohort and for patients with adenocarcinoma (ACA) and large cell carcinoma (LCC). Targeted cancer therapies blocking SDF-1/CXCR4 interaction already exist, and our data suggest that expression of SDF-1, especially on poorer prognosis subgroups of LCC and ACA, indicates patients that might benefit more than others. This should be taken into account when assessing the effectiveness of such targeted approaches for NSCLC patients and could lead to important implications.
authors.affiliation: Institute of Pathology, Hospital Bayreuth, Preuschwitzerstrasse 101, Bayreuth, 95445, Germany. william.sterlacci@klinikum-bayreuth.de.
authors.forename: William
authors.initials: W
authors.lastname: Sterlacci
authors.affiliation: Institute of Pathology, Hospital Bayreuth, Preuschwitzerstrasse 101, Bayreuth, 95445, Germany.
authors.forename: Shereen
authors.initials: S
authors.lastname: Saker
authors.affiliation: Institute of Pathology, University Hospital Basel, Schoenbeinstrasse 40, Basel, 4031, Switzerland.
authors.forename: Bettina
authors.initials: B
authors.lastname: Huber
authors.affiliation: Department of Internal Medicine, Oncology and Geriatrics, Hospital Hochrum, Lärchenstrasse 41, Rum bei Innsbruck, 6063, Austria.|Department of Internal Medicine, Division of Hematology and Oncology, Medical University Innsbruck, Anichstrasse 35, Innsbruck, 6020, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Fiegl
authors.affiliation: Institute of Pathology, University Hospital Basel, Schoenbeinstrasse 40, Basel, 4031, Switzerland.
authors.forename: Alexandar
authors.initials: A
authors.lastname: Tzankov
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality; D000077192:Adenocarcinoma of Lung; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D018287:Carcinoma, Large Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D054377:Chemokine CXCL12 / Q000032:analysis / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12
keywords: CXCR4; Non-small cell lung cancer; Prognosis; SDF-1
references.citation: Am J Respir Cell Mol Biol. 2004 May;30(5):671-7
references.pmid: 14672915
references.citation: Lung Cancer. 2010 Mar;67(3):257-74
references.pmid: 19914732
references.citation: Cytokine Growth Factor Rev. 2010 Aug;21(4):253-62
references.pmid: 20434943
references.citation: J Thorac Cardiovasc Surg. 2009 Mar;137(3):615-21
references.pmid: 19258077
references.citation: Nat Commun. 2013;4:1795
references.pmid: 23653207
references.citation: Am J Respir Crit Care Med. 2003 Jun 15;167(12):1676-86
references.pmid: 12626353
references.citation: CA Cancer J Clin. 2012 Jul-Aug;62(4):220-41
references.pmid: 22700443
references.citation: Am J Clin Pathol. 2011 Apr;135(4):611-8
references.pmid: 21411784
references.citation: Expert Opin Investig Drugs. 2003 Feb;12(2):185-95
references.pmid: 12556213
references.citation: Cell Signal. 2009 Nov;21(11):1595-606
references.pmid: 19586611
references.citation: J Clin Invest. 2010 Mar;120(3):694-705
references.pmid: 20179352
references.citation: Breast Cancer Res Treat. 2010 Oct;123(3):733-45
references.pmid: 20020198
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16281-6
references.pmid: 19805294
references.citation: Eur J Cardiothorac Surg. 2012 Feb;41(2):368-75
references.pmid: 21683606
references.citation: J Thorac Cardiovasc Surg. 2012 Nov;144(5):1167-1175.e1
references.pmid: 22925564
references.citation: Ann Oncol. 2004 Apr;15(4):613-7
references.pmid: 15033669
references.citation: Hum Pathol. 2008 Dec;39(12):1751-5
references.pmid: 18701133
references.citation: Cancer Res. 2002 Nov 1;62(21):6304-11
references.pmid: 12414661
references.citation: Virchows Arch. 2015 Jul;467(1):55-66
references.pmid: 25854914
references.citation: Exp Cell Res. 2011 Mar 10;317(5):575-89
references.pmid: 21223965
references.citation: J Cell Biol. 1996 Jan;132(1-2):239-49
references.pmid: 8567727
references.citation: J Thorac Oncol. 2011 Jul;6(7):1169-78
references.pmid: 21623238
references.citation: Oncogene. 2006 Aug 17;25(36):4986-97
references.pmid: 16568088
references.citation: Hum Pathol. 2012 Mar;43(3):339-49
references.pmid: 21840566
references.citation: Biochem Pharmacol. 2007 Dec 15;74(12):1702-12
references.pmid: 17904532
references.citation: J Thorac Cardiovasc Surg. 2011 Jun;141(6):1503-12
references.pmid: 21463876
references.citation: Virchows Arch. 2009 Aug;455(2):125-32
references.pmid: 19652998
references.citation: Eur J Cancer. 2009 Sep;45(14 ):2473-87
references.pmid: 19596191
references.citation: Nat Rev Clin Oncol. 2011 Feb;8(2):68-70
references.pmid: 21278771
references.citation: Onco Targets Ther. 2013 Sep 30;6:1347-61
references.pmid: 24124379
references.citation: J Immunol. 2006 Nov 15;177(10):6983-90
references.pmid: 17082613
references.citation: Br J Cancer. 2012 Jul 24;107(3):491-500
references.pmid: 22722314
references.citation: Lung Cancer. 2015 Feb;87(2):193-200
references.pmid: 25564398
references.citation: Int J Oncol. 2008 Jul;33(1):113-9
references.pmid: 18575756
references.citation: Leukemia. 2014 Mar;28(3):566-76
references.pmid: 23817178
references.citation: Pharmacol Rev. 2000 Mar;52(1):145-76
references.pmid: 10699158
references.citation: Nat Rev Cancer. 2004 Jul;4(7):540-50
references.pmid: 15229479
references.citation: Clin Cancer Res. 2005 Dec 1;11(23):8273-80
references.pmid: 16322285
references.citation: Leuk Lymphoma. 2010 Feb;51(2):199-212
references.pmid: 19925052
references.citation: Theranostics. 2013;3(1):26-33
references.pmid: 23382783
references.citation: Immunity. 2000 Feb;12(2):121-7
references.pmid: 10714678
references.citation: J Thorac Oncol. 2014 Jan;9(1):41-9
references.pmid: 24346092
references.citation: Ann Hematol. 2003 Aug;82(8):500-5
references.pmid: 12783211
references.citation: Blood. 2011 Jan 20;117(3):882-9
references.pmid: 21079155