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.
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.
Nordfors
Kristiina
K
Department of Pathology, Tampere University Hospital, Tampere, Finland. kristiina.nordfors@gmail.com
Haapasalo
Joonas
J
Korja
Miikka
M
Niemelä
Anssi
A
Laine
Jukka
J
Parkkila
Anna-Kaisa
AK
Pastorekova
Silvia
S
Pastorek
Jaromir
J
Waheed
Abdul
A
Sly
William S
WS
Parkkila
Seppo
S
Haapasalo
Hannu
H
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
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
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