title: The tumour-associated carbonic anhydrases CA II, CA IX and CA XII in a group of medulloblastomas and supratentorial primitive neuroectodermal tumours: an association of CA IX with poor prognosis.
abstract: BACKGROUND
  Medulloblastomas (MBs) and supratentorial primitive neuroectodermal tumours (PNETs) are the most common highly aggressive paediatric brain tumours. In spite of extensive research on these tumours, there are only few known biomarkers or therapeutic target proteins, and the prognosis of patients with these tumours remains poor. Our aim was to investigate whether carbonic anhydrases (CAs), enzymes commonly overexpressed in various tumours including glioblastomas and oligodendrogliomas, are present in MBs and PNETs, and whether their expression can be correlated with patient prognosis.
  
  
  METHODS
  We determined the expression of the tumour-associated carbonic anhydrases CA II, CA IX and CA XII in a series of MB/PNET specimens (n = 39) using immunohistochemistry.
  
  
  RESULTS
  Endothelial CA II, cytoplasmic CA II, CA IX and CA XII were expressed in 49%, 73%, 23% and 11% of the tumours, respectively. CA II was detected in the neovessel endothelium and the tumour cell cytoplasm. CA IX was mainly expressed in the tumour cells located in perinecrotic areas. CA XII showed the most homogenous distribution within the tumours. Importantly, CA IX expression predicted poor prognosis in both univariate (p = 0.041) and multivariate analyses (p = 0.016).
  
  
  CONCLUSIONS
  We suggest that CA IX should be considered a potential prognostic and therapeutic target in MBs and PNETs.
authors.affiliation: Department of Pathology, Tampere University Hospital, Tampere, Finland. kristiina.nordfors@gmail.com
authors.forename: Kristiina
authors.initials: K
authors.lastname: Nordfors
authors.forename: Joonas
authors.initials: J
authors.lastname: Haapasalo
authors.forename: Miikka
authors.initials: M
authors.lastname: Korja
authors.forename: Anssi
authors.initials: A
authors.lastname: Niemelä
authors.forename: Jukka
authors.initials: J
authors.lastname: Laine
authors.forename: Anna-Kaisa
authors.initials: AK
authors.lastname: Parkkila
authors.forename: Silvia
authors.initials: S
authors.lastname: Pastorekova
authors.forename: Jaromir
authors.initials: J
authors.lastname: Pastorek
authors.forename: Abdul
authors.initials: A
authors.lastname: Waheed
authors.forename: William S
authors.initials: WS
authors.lastname: Sly
authors.forename: Seppo
authors.initials: S
authors.lastname: Parkkila
authors.forename: Hannu
authors.initials: H
authors.lastname: Haapasalo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D024402:Carbonic Anhydrase II / Q000032:analysis*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000032:analysis*; D002528:Cerebellar Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology / Q000628:therapy; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D003593:Cytoplasm / Q000201:enzymology; D042783:Endothelial Cells / Q000201:enzymology; D005260:Female; D005387:Finland; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D008527:Medulloblastoma / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology / Q000628:therapy; D008875:Middle Aged; D018242:Neuroectodermal Tumors, Primitive / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology / Q000628:therapy; D016017:Odds Ratio; D016016:Proportional Hazards Models; D015173:Supratentorial Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology / Q000628:therapy; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D024402:Carbonic Anhydrase II; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; C477378:carbonic anhydrase XII
references.citation: Neuropathol Appl Neurobiol. 2000 Dec;26(6):504-12
references.pmid: 11123716
references.citation: Cancer Biol Ther. 2007 Jan;6(1):70-5
references.pmid: 17172824
references.citation: Cancer Res. 1998 Mar 1;58(5):896-9
references.pmid: 9500446
references.citation: Mol Hum Reprod. 2000 Jan;6(1):68-74
references.pmid: 10611263
references.citation: J Histochem Cytochem. 1983 Jul;31(7):879-86
references.pmid: 6406590
references.citation: Int J Oncol. 2006 Oct;29(4):1025-33
references.pmid: 16964400
references.citation: Bioorg Med Chem. 2001 Mar;9(3):703-14
references.pmid: 11310605
references.citation: BMC Cancer. 2008 Jan 04;8:1
references.pmid: 18173856
references.citation: Histopathology. 2006 Dec;49(6):594-602
references.pmid: 17163844
references.citation: J Clin Oncol. 2005 Oct 20;23(30):7621-31
references.pmid: 16234523
references.citation: Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2220-4
references.pmid: 10688890
references.citation: Int J Cancer. 2003 Jul 20;105(6):873-81
references.pmid: 12767076
references.citation: Cancer Immun. 2007 Aug 17;7:14
references.pmid: 17705350
references.citation: Cancer Res. 2006 May 15;66(10):5190-200
references.pmid: 16707443
references.citation: Cancer Biol Ther. 2005 Oct;4(10):1055-62
references.pmid: 16294030
references.citation: Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7608-13
references.pmid: 9636197
references.citation: Clin Cancer Res. 2006 Jan 15;12(2):473-7
references.pmid: 16428489
references.citation: Int J Radiat Oncol Biol Phys. 2006 May 1;65(1):246-54
references.pmid: 16618579
references.citation: Exp Cell Res. 2003 Nov 1;290(2):332-45
references.pmid: 14567991
references.citation: Neuro Oncol. 2007 Jul;9(3):308-13
references.pmid: 17435181
references.citation: Cancer Metastasis Rev. 1987;5(4):343-65
references.pmid: 2882864
references.citation: Int J Cancer. 2008 Jul 15;123(2):395-400
references.pmid: 18464292
references.citation: J Pathol. 1994 Dec;174(4):275-82
references.pmid: 7884589
references.citation: Acta Neuropathol. 2007 Aug;114(2):97-109
references.pmid: 17618441
references.citation: Clin Cancer Res. 2005 Nov 15;11(22):8201-7
references.pmid: 16299253
references.citation: Neuro Oncol. 2008 Apr;10(2):131-8
references.pmid: 18322268
references.citation: Acta Neuropathol. 1994;88(6):520-6
references.pmid: 7879598
references.citation: Acta Neuropathol. 2006 Jul;112(1):5-12
references.pmid: 16685513
references.citation: Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12596-601
references.pmid: 9770531
references.citation: Biochem J. 2005 Nov 15;392(Pt 1):83-92
references.pmid: 16083424
references.citation: Expert Opin Investig Drugs. 2003 Feb;12(2):283-7
references.pmid: 12556221
references.citation: J Biol Chem. 2008 Oct 10;283(41):27799-27809
references.pmid: 18703501
references.citation: Cancer Res. 2009 Jan 1;69(1):358-68
references.pmid: 19118021
references.citation: Nat Rev Drug Discov. 2008 Feb;7(2):168-81
references.pmid: 18167490
references.citation: Am J Pathol. 2000 Feb;156(2):577-84
references.pmid: 10666387
references.citation: Neurol India. 2006 Mar;54(1):16-23
references.pmid: 16679637
references.citation: BMC Dev Biol. 2006 May 23;6:22
references.pmid: 16719910
references.citation: Histochemistry. 1993 Jan;99(1):37-41
references.pmid: 8468192
references.citation: J Enzyme Inhib Med Chem. 2004 Jun;19(3):199-229
references.pmid: 15499993
references.citation: J Neurosurg. 1994 Nov;81(5):690-8
references.pmid: 7931615
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16233-8
references.pmid: 19805286
references.citation: Int J Radiat Oncol Biol Phys. 2008 Dec 1;72(5):1319-23
references.pmid: 18485615
references.citation: Br J Cancer. 1996 Mar;73(5):620-3
references.pmid: 8605096
references.citation: Virology. 1992 Apr;187(2):620-6
references.pmid: 1312272
references.citation: J Neurobiol. 2005 Sep 15;64(4):458-75
references.pmid: 16041741
references.citation: J Clin Oncol. 1995 Jan;13(1):112-23
references.pmid: 7799011
references.citation: World J Gastroenterol. 2005 Jan 14;11(2):155-63
references.pmid: 15633208
references.citation: Br J Neurosurg. 2009 Aug;23(4):364-75
references.pmid: 19637007
references.citation: Semin Oncol. 2004 Oct;31(5):666-75
references.pmid: 15497120
references.citation: Blood. 2006 Dec 15;108(13):4109-17
references.pmid: 16931630
references.citation: J Urol. 2004 Dec;172(6 Pt 1):2158-61
references.pmid: 15538222
references.citation: Annu Rev Biochem. 1995;64:375-401
references.pmid: 7574487
references.citation: Cancer Res. 2000 Dec 15;60(24):7075-83
references.pmid: 11156414
references.citation: Neuro Oncol. 2005 Oct;7(4):465-75
references.pmid: 16212811
references.citation: Adv Clin Chem. 2006;42:167-216
references.pmid: 17131627
references.citation: J Pediatr Hematol Oncol. 1998 Nov-Dec;20(6):520-7
references.pmid: 9856671