Carbonic anhydrases in meningiomas: association of endothelial carbonic anhydrase II with aggressive tumor features.
OBJECTIVE
Carbonic anhydrase (CA) II and IX are enzymes involved in pH homeostasis and have been shown to be upregulated in several types of cancer. In this study, the authors evaluate the expression of CA II and IX in meningiomas and assess their relationship to patient age, tumor type and grade, tumor sex hormone receptor status, tumor cell proliferation, and tumor recurrence.


METHODS
This study was conducted in consecutive patients who underwent meningioma surgeries at Tampere University Hospital between 1989 and 1999. The expression of CA II and IX was studied immunohistochemically using a tissue microarray technique and specific antibodies.


RESULTS
Immunohistological staining with CA II and IX was assessed in 443 primary and 67 recurrent tumor specimens. Of these samples, 455 were benign (WHO Grade I), 49 atypical (Grade II), and 6 malignant (Grade III). Endothelial cells in 14.8% of the tumors stained positively for CA II. Tumor cells were positive for CA IX in 11.6% of the cases. Endothelial CA II expression correlated with increasing histological grade (p=0.002), and tumor proliferation rates were higher in CA II+ versus CA II- cases (p=0.002). Androgen receptor-negative tumors were found to be CA II+ significantly more often than androgen receptor-positive tumors (p=0.001). No associations were found with the CA IX enzyme.


CONCLUSIONS
Carbonic anhydrase II positivity in the endothelium was associated with cell proliferation and malignancy grade. These results suggest that CA II expression is associated with malignant progression of meningiomas and could thus be a target molecule for anticancer therapy.
Korhonen
Katariina
K
Orton Orthopaedic Hospital, Invalid Foundation, Helsinki, Finland. katariina.korhonen@invalidisaatio.fi
Parkkila
Anna-Kaisa
AK
Helen
Pauli
P
Välimäki
Ritva
R
Pastorekova
Silvia
S
Pastorek
Jaromir
J
Parkkila
Seppo
S
Haapasalo
Hannu
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024402:Carbonic Anhydrase II / Q000032:analysis*; D002256:Carbonic Anhydrases / Q000032:analysis; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008577:Meningeal Neoplasms / Q000201:enzymology* / Q000473:pathology; D008579:Meningioma / Q000201:enzymology* / Q000473:pathology; D008875:Middle Aged; D011944:Receptors, Androgen / Q000032:analysis
D011944:Receptors, Androgen; D024402:Carbonic Anhydrase II; D002256:Carbonic Anhydrases