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

BMC Cancer. 2010 Apr 18:10:148. doi: 10.1186/1471-2407-10-148.

Abstract

Background: Medulloblastomas (MBs) and supratentorial primitive neuroectodermal tumours (PNETs) are the most common highly aggressive paediatric brain tumours. In spite of extensive research on these tumours, there are only few known biomarkers or therapeutic target proteins, and the prognosis of patients with these tumours remains poor. Our aim was to investigate whether carbonic anhydrases (CAs), enzymes commonly overexpressed in various tumours including glioblastomas and oligodendrogliomas, are present in MBs and PNETs, and whether their expression can be correlated with patient prognosis.

Methods: 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.

Results: 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).

Conclusions: We suggest that CA IX should be considered a potential prognostic and therapeutic target in MBs and PNETs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, Neoplasm / analysis*
  • Apoptosis
  • Biomarkers, Tumor / analysis*
  • Carbonic Anhydrase II / analysis*
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / analysis*
  • Cerebellar Neoplasms / blood supply
  • Cerebellar Neoplasms / enzymology*
  • Cerebellar Neoplasms / pathology
  • Cerebellar Neoplasms / therapy
  • Chi-Square Distribution
  • Child
  • Child, Preschool
  • Cytoplasm / enzymology
  • Endothelial Cells / enzymology
  • Female
  • Finland
  • Humans
  • Immunohistochemistry
  • Infant
  • Infant, Newborn
  • Kaplan-Meier Estimate
  • Male
  • Medulloblastoma / blood supply
  • Medulloblastoma / enzymology*
  • Medulloblastoma / pathology
  • Medulloblastoma / therapy
  • Middle Aged
  • Neuroectodermal Tumors, Primitive / blood supply
  • Neuroectodermal Tumors, Primitive / enzymology*
  • Neuroectodermal Tumors, Primitive / pathology
  • Neuroectodermal Tumors, Primitive / therapy
  • Odds Ratio
  • Proportional Hazards Models
  • Supratentorial Neoplasms / blood supply
  • Supratentorial Neoplasms / enzymology*
  • Supratentorial Neoplasms / pathology
  • Supratentorial Neoplasms / therapy
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Carbonic Anhydrase II
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases
  • carbonic anhydrase XII