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Carbonic anhydrase II in the endothelium of glial tumors: A potential target for therapy

Department of Pathology, Centre for Laboratory Medicine, Tampere University Hospital, FI-33520 Tampere, Finland (J.H., K.N., S.J., H.B., I.R., H.H.); Department of Neurology, Tampere University Hospital, FI-33521 Tampere, Finland (A.-K.P.); Institute of Medical Technology, University of Tampere and Tampere University Hospital, FI-33520 Tampere, Finland (S.P.); and Faculty of Medicine, University of Turku, FI-20520 Turku, Finland (J.H., K.N.)

Address correspondence to Seppo Parkkila, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Biokatu 6, FIN-33520 Tampere, Finland (seppo.parkkila{at}uta.fi).

Carbonic anhydrase isozyme II (CA II) is a cytosolic enzyme that is highly expressed in most organs, including the brain, where it is mainly located in the oligodendrocytes. Recent studies have shown that its expression is induced in the endothelium of neovessels in melanoma and esophageal, renal, and lung cancer. Immunological studies further indicate that CA II represents a major target antigen stimulating an autoantibody response in melanoma patients. These results prompted us to investigate endothelial CA II expression in two types of brain cancer: oligodendrogliomas and astrocytomas. A series of 255 astrocytoma and 71 oligodendroglial tumor specimens was immunostained for CA II. The staining results were correlated with a number of different clinicopathological factors and survival data. CA II showed weak or no expression in low-grade tumors, while grade 3 mixed oligoastrocytoma and glioblastoma multiforme were the most positively stained tumor types. Survival analysis indicated that endothelial CA II staining is significantly associated with a poor prognosis in patients with astrocytomas. About 17% of patients with CA II-negative tumors (weak or no endothelial signal) were still alive at the end of the follow-up period of five years. The presence of CA II in the tumor endothelium suggests that it may play an important functional role in tumor metabolism. From a clinical perspective, the results also open new avenues for selecting tumor types for dendritic cell therapy trials.

Key Words: brain • cancer • carbonic anhydrase • endothelium • tumor

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