Carbonic anhydrase XII (CA XII) is a transmembrane
enzyme that is associated with neoplastic growth. CA XII has been proposed to be involved in acidification of the extracellular milieu, creating an appropriate microenvironment for rapid
tumor growth. Because RNA sequence databases have indicated that two
isoforms of CA XII might exist in human tissues, and because alternatively spliced
protein forms have been linked to aggressive behavior of
cancer cells, we designed a study to evaluate the presence of the two forms of CA XII in diffuse
astrocytomas, a
tumor type known for its aggressive and often noncurable behavior. Reverse transcription PCR of
tumor samples surprisingly revealed that CA XII present in diffuse
astrocytomas is mainly encoded by a shorter
mRNA variant. We further showed by Western blotting that anti-CA XII antibody recognized both
isoforms in the
glioblastoma cell lines, and we then evaluated the expression of CA XII in
astrocytomas using immunohistochemistry and correlated the results with various clinicopathological and molecular factors. Of 370 diffusely infiltrating
astrocytomas, 363 cases (98%) showed immunoreactions for CA XII. Importantly, CA XII expression correlated with poorer patient prognosis in univariate (p = 0.010, log-rank test) and multivariate survival analyses (p = 0.039, Cox analysis). From these results, we conclude that CA XII is commonly expressed in diffuse
astrocytomas and that it might be used as a
biomarker of poor prognosis. The absence of 11
amino acids in the shorter
isoform, which seems to be common in
astrocytomas, may affect the normal quaternary structure and biological function of CA XII.