title: Are morphological criteria sufficient for the identification of circulating tumor cells in renal cancer?
abstract: BACKGROUND
  Single circulating tumor cells (CTCs) or circulating tumor microemboli (CTMs) are potential biomarkers of renal cell cancer (RCC), however studies of CTCs/CTMs in RCC are limited. In this pilot study we aimed to evaluate a novel blood filtration technique suited for cytomorphological classification, immunocytochemical and molecular characterization of filtered, so called circulating non-hematologic cells (CNHCs) - putative CTCs/CTMs - in patients with RCC.
  
  
  METHODS
  Blood of 40 patients with renal tumors was subjected to ScreenCell filtration. CNHCs were classified according to cytomorphological criteria. Immunocytochemical analysis was performed with antibodies against CD45, CD31 and carbonic anhydrase IX (CAIX, a RCC marker). DNA of selected CNHCs and respective primary tumors was analysed by array-CGH.
  
  
  RESULTS
  CNHC-clusters with malignant or uncertain malignant cytomorphological features - putative CTMs - were negative for CD45, positive for CD31, while only 6% were CAIX positive. Array-CGH revealed that 83% of malignant and uncertain malignant cells did represent with a balanced genome whereas 17% presented genomic DNA imbalances which did not match the aberrations of the primary tumors. Putative single CTCs were negative for CD45, 33% were positive for CD31 and 56% were positive for CAIX.
  
  
  CONCLUSIONS
  The majority of CNHC-clusters, putative CTMs, retrieved by ScreenCell filtration may be of endothelial origin. Morphological criteria seem to be insufficient to distinguish malignant from non-malignant cells in renal cancer.
authors.affiliation: Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, Graz, 8036, Austria. karoline.lackner@medunigraz.at.
authors.forename: Amin
authors.initials: A
authors.lastname: El-Heliebi
authors.forename: Thomas
authors.initials: T
authors.lastname: Kroneis
authors.forename: Evelyn
authors.initials: E
authors.lastname: Zöhrer
authors.forename: Johannes
authors.initials: J
authors.lastname: Haybaeck
authors.forename: Katja
authors.initials: K
authors.lastname: Fischereder
authors.forename: Karin
authors.initials: K
authors.lastname: Kampel-Kettner
authors.forename: Richard
authors.initials: R
authors.lastname: Zigeuner
authors.forename: Hannelore
authors.initials: H
authors.lastname: Pock
authors.forename: Regina
authors.initials: R
authors.lastname: Riedl
authors.forename: Rudolf
authors.initials: R
authors.lastname: Stauber
authors.forename: Jochen Bernd
authors.initials: JB
authors.lastname: Geigl
authors.forename: Berthold
authors.initials: B
authors.lastname: Huppertz
authors.forename: Peter
authors.initials: P
authors.lastname: Sedlmayr
authors.forename: Carolin
authors.initials: C
authors.lastname: Lackner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002452:Cell Count; D048430:Cell Shape; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D004273:DNA, Neoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000473:pathology*; D061346:Laser Capture Microdissection; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D019408:Platelet Endothelial Cell Adhesion Molecule-1
references.citation: Nucleic Acids Res. 2007;35(3):e15
references.pmid: 17178751
references.citation: Anticancer Res. 2011 Feb;31(2):427-41
references.pmid: 21378321
references.citation: Eur J Cancer. 2005 Dec;41(18):2935-47
references.pmid: 16310354
references.citation: Expert Opin Ther Targets. 2012 Dec;16(12):1215-25
references.pmid: 22978444
references.citation: Oncogene. 2004 Jul 22;23(33):5624-31
references.pmid: 15184875
references.citation: Angiogenesis. 2009;12(1):69-79
references.pmid: 19212818
references.citation: Cell. 2012 Mar 2;148(5):873-85
references.pmid: 22385957
references.citation: Genes Chromosomes Cancer. 1996 Dec;17(4):199-204
references.pmid: 8946201
references.citation: Br J Cancer. 2011 Sep 6;105(6):847-53
references.pmid: 21829190
references.citation: Int J Cancer. 2012 Aug 15;131(4):E405-15
references.pmid: 21935921
references.citation: J Clin Oncol. 2009 Aug 1;27(22):3584-90
references.pmid: 19487381
references.citation: Breast Cancer Res Treat. 2011 Dec;130(3):809-16
references.pmid: 21311967
references.citation: Cancer Cell. 2008 Sep 9;14(3):263-73
references.pmid: 18772115
references.citation: Genes Chromosomes Cancer. 2003 Apr;36(4):361-74
references.pmid: 12619160
references.citation: Transl Oncol. 2013 Feb;6(1):51-65
references.pmid: 23418617
references.citation: J Transl Med. 2012 Nov 13;10:222
references.pmid: 23146106
references.citation: Science. 2006 Sep 22;313(5794):1785-7
references.pmid: 16990548
references.citation: Breast Cancer Res Treat. 2011 Nov;130(2):449-55
references.pmid: 21298334
references.citation: BJU Int. 2012 Jan;109(2):200-6
references.pmid: 22212284
references.citation: Hepatology. 2004 Mar;39(3):792-7
references.pmid: 14999698
references.citation: Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14608-13
references.pmid: 11121063
references.citation: Br J Cancer. 2006 Jan 30;94(2):333-7
references.pmid: 16333309
references.citation: Am J Med Genet A. 2006 Dec 15;140(24):2757-67
references.pmid: 17103431
references.citation: Arch Pathol Lab Med. 2007 Aug;131(8):1290-7
references.pmid: 17683191
references.citation: N Engl J Med. 2012 Mar 8;366(10):883-892
references.pmid: 22397650
references.citation: Am J Pathol. 2000 Jan;156(1):57-63
references.pmid: 10623654
references.citation: Recent Results Cancer Res. 2012;195:163-70
references.pmid: 22527503
references.citation: Biomed Microdevices. 2011 Feb;13(1):203-13
references.pmid: 20978853
references.citation: Mol Hum Reprod. 2004 Apr;10(4):283-9
references.pmid: 14985479
references.citation: Cancer Lett. 2007 Aug 18;253(2):180-204
references.pmid: 17314005
references.citation: Hum Pathol. 2006 Jun;37(6):711-8
references.pmid: 16733212
references.citation: Am J Surg Pathol. 2009 Feb;33(2):241-7
references.pmid: 18941400
references.citation: Am J Clin Pathol. 2011 Jan;135(1):146-56
references.pmid: 21173137
references.citation: J Thorac Oncol. 2012 Feb;7(2):306-15
references.pmid: 22173704
references.citation: Annu Rev Immunol. 1989;7:339-69
references.pmid: 2523715
references.citation: Curr Oncol Rep. 2012 Jun;14(3):221-9
references.pmid: 22434312
references.citation: Acta Clin Belg. 2011 Sep-Oct;66(5):332-6
references.pmid: 22145267
references.citation: Nucleic Acids Res. 2008 Aug;36(13):e80
references.pmid: 18559357
references.citation: Clin Cancer Res. 2001 Dec;7(12):4080-5
references.pmid: 11751505
references.citation: Oncology. 2011;81(3-4):199-205
references.pmid: 22067898
references.citation: Cancer Chemother Pharmacol. 2011 Sep;68(3):763-8
references.pmid: 21170650
references.citation: J Clin Endocrinol Metab. 2013 Sep;98(9):3731-8
references.pmid: 23836937
references.citation: Am J Pathol. 2001 Mar;158(3):905-19
references.pmid: 11238039
references.citation: Br J Cancer. 2012 Jan 31;106(3):508-16
references.pmid: 22187035
references.citation: Nucleic Acids Res. 2009 Aug;37(15):e105
references.pmid: 19541849
references.citation: J Urol. 2012 Jul;188(1):21-6
references.pmid: 22578722
references.citation: J Transl Med. 2012 Jul 02;10:138
references.pmid: 22747748
references.citation: Gastroenterology. 2010 May;138(5):1714-26
references.pmid: 20100481
references.citation: J Clin Oncol. 2013 Jun 20;31(18):2273-81
references.pmid: 23669222
references.citation: Bioinformatics. 2001 Dec;17(12):1228-9
references.pmid: 11751233
references.citation: Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21677-82
references.pmid: 21098274
references.citation: Nat Protoc. 2007;2(12):3173-84
references.pmid: 18079717
references.citation: J Clin Oncol. 2009 Feb 10;27(5):746-53
references.pmid: 19124809
references.citation: Mod Pathol. 2003 Oct;16(10):1053-9
references.pmid: 14559990
references.citation: J Clin Oncol. 2012 Feb 10;30(5):525-32
references.pmid: 22253462
references.citation: Clin Cancer Res. 2011 Feb 15;17(4):827-35
references.pmid: 21098695
references.citation: Eur J Cancer. 2010 Jul;46(11):2027-35
references.pmid: 20399640
references.citation: BMC Cancer. 2010 Dec 31;10:695
references.pmid: 21194438
references.citation: Clin Chem. 2012 May;58(5):936-40
references.pmid: 22205690
references.citation: J Invest Dermatol. 2010 Oct;130(10):2440-7
references.pmid: 20535130
references.citation: J Clin Pathol. 1990 Sep;43(9):752-7
references.pmid: 2212067
references.citation: Nucleic Acids Res. 2008 Apr;36(7):e39
references.pmid: 18344524
references.citation: J Urol. 2011 Nov;186(5):1773-7
references.pmid: 21944989
references.citation: Cancer Res. 2006 Sep 1;66(17):8319-26
references.pmid: 16951136
references.citation: Cancer Res. 2013 Jan 1;73(1):8-11
references.pmid: 23271724
references.citation: Am J Hematol. 2008 Jul;83(7):540-6
references.pmid: 18161787
references.citation: J Clin Oncol. 2009 Jul 10;27(20):3312-8
references.pmid: 19451442
references.citation: Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18392-7
references.pmid: 20930119