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

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.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).We suggest that CA IX should be considered a potential prognostic and therapeutic target in MBs and PNETs.Medulloblastomas (MBs) and primitive neuroectodermal tumours (PNETs) are classified as embryonal tumours of the central nervous system (CNS) and histologically correspond to WHO grade IV [1]. One viewpoint postulates that these tumours show a common ontogeny, arising from related progenitor cells that have the potential for divergent neuroepithelial differentation. However, in recent years molecular genetic analyses have demonstrated different genetic profiles for these tumours [1]. It has been proposed that MBs originate from the neoplastic transformation of granule cell precursors in the cerebellum via deregulation of molecular pathways involved in normal cerebellar development [2,3]. Correspondingly, PNETs arise in the cerebral hemispheres, brain stem or spinal cord. The neuroepithelial tumour cells of a PNET may be undifferentiated or poorly differentiated. In addition, the tumour cells may have aberrant differentiations, including neuronal, astrocytic and ependymal lines.MB is the most common childhood malignant tumour of the central nervous system and accounts for 12-25% of all paediatric CNS tumours. It is very rare in adults, accounting for only 0.5-1% of brain tumours [4]. The main defective cell signalling pathways involved