Expression of carbonic anhydrase IX in astrocytic tumors predicts poor prognosis.
OBJECTIVE
Carbonic anhydrase IX (CA IX) is a hypoxia-inducible enzyme, which is associated with neoplastic growth. Ectopic CA IX expression has been observed in several tumors, whose normal counterparts do not express this enzyme. Normal human brain tissue shows only slight or no expression of CA IX.


METHODS
We describe CA IX expression in human diffusely infiltrating astrocytomas. The association of CA IX is evaluated with clinicopathologic and molecular factors including cell proliferation and apoptosis as well as the expression of p53 and epidermal growth factor receptor.


RESULTS
CA IX immunopositivity was observed in 284 cases of 362 (78%) tumors. The positive areas were often located in close proximity to necrotic regions (P < 0.001). The CA IX immunoreactivity showed strong association with tumor malignancy grades (P < 0.0001). CA IX showed no association with p53 expression nor did it correlate with epidermal growth factor receptor-amplification, apoptosis, or cell proliferation. CA IX intensity had significant prognostic value in univariate (P=0.0011, log-rank test) and multivariate survival analysis (P = 0.038, Cox analysis).


CONCLUSIONS
CA IX expression is common in diffusely infiltrating high-grade astrocytomas. Our results suggest that CA IX is a useful biomarker for predicting poor prognosis of astrocytic tumors. It may also be a promising target molecule for the improvement of therapeutic interventions in astrocytomas.
Haapasalo
Joonas A
JA
Department of Pathology, Centre for Laboratory Medicine, Tampere University Hospital, FIN-33521 Tampere, Finland.
Nordfors
Kristiina M
KM
Hilvo
Mika
M
Rantala
Immo J
IJ
Soini
Ylermi
Y
Parkkila
Anna-Kaisa
AK
Pastoreková
Silvia
S
Pastorek
Jaromir
J
Parkkila
Seppo M
SM
Haapasalo
Hannu K
HK
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D001254:Astrocytoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases