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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.

Nordfors K, Haapasalo J, Korja M, Niemelä A, Laine J, Parkkila AK, Pastorekova S, Pastorek J, Waheed A, Sly WS, Parkkila S, Haapasalo H - BMC Cancer (2010)

Bottom Line: Medulloblastomas (MBs) and supratentorial primitive neuroectodermal tumours (PNETs) are the most common highly aggressive paediatric brain 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Tampere University Hospital, Tampere, Finland. kristiina.nordfors@gmail.com

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.

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Kaplan-Meier curves showing overall survival of patients with MB or PNET categorised by: A. tumour cell-associated CA II, B. endothelial CA II, C. CA IX (p = 0.041; log-rank test), and D. CA XII immunostaining results.
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Figure 2: Kaplan-Meier curves showing overall survival of patients with MB or PNET categorised by: A. tumour cell-associated CA II, B. endothelial CA II, C. CA IX (p = 0.041; log-rank test), and D. CA XII immunostaining results.

Mentions: All 35 patients with primary MB/PNET were included in the survival analysis (Figure 2). The patients with a CA IX-positive MB/PNET had a worse prognosis than those who had a CA IX-negative tumour (all tumours p = 0.041, MBs p = 0.030, PNETs p = n.s.; log-rank test; Figure 2). We also found a correlation between survival and CA XII staining in patients with MB. The patients with CA XII-positive tumours showed significantly worse prognosis (p = 0.010, log-rank test). There was no significant difference in survival time between the histological subgroups (p = 0.463, log-rank test). Of the prognostic indicators used for MBs in the current WHO classification, (2007) the following variables were included into the Cox multivariate survival analysis: patient age, MIB-1 proliferation index, apoptosis index and expression of p53, c-erbB-2 and bcl-2. In addition, the histopathological group (MB vs. supratentorial PNET), CA II, CA IX and CA XII were used in the analysis. These variables were grouped as presented in Table 2. In the Cox analysis, only expression of CA IX (odds ratio 4.31; 95% confidence interval (CI) 1.31 - 14.11; p = 0.016) and the apoptosis index (odds ratio 3.29; 95% CI 1.05 - 10.31, p = 0.041) were independent prognostic factors. The expression of either CA II and CA XII failed to show any significant association with survival.


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.

Nordfors K, Haapasalo J, Korja M, Niemelä A, Laine J, Parkkila AK, Pastorekova S, Pastorek J, Waheed A, Sly WS, Parkkila S, Haapasalo H - BMC Cancer (2010)

Kaplan-Meier curves showing overall survival of patients with MB or PNET categorised by: A. tumour cell-associated CA II, B. endothelial CA II, C. CA IX (p = 0.041; log-rank test), and D. CA XII immunostaining results.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2874782&req=5

Figure 2: Kaplan-Meier curves showing overall survival of patients with MB or PNET categorised by: A. tumour cell-associated CA II, B. endothelial CA II, C. CA IX (p = 0.041; log-rank test), and D. CA XII immunostaining results.
Mentions: All 35 patients with primary MB/PNET were included in the survival analysis (Figure 2). The patients with a CA IX-positive MB/PNET had a worse prognosis than those who had a CA IX-negative tumour (all tumours p = 0.041, MBs p = 0.030, PNETs p = n.s.; log-rank test; Figure 2). We also found a correlation between survival and CA XII staining in patients with MB. The patients with CA XII-positive tumours showed significantly worse prognosis (p = 0.010, log-rank test). There was no significant difference in survival time between the histological subgroups (p = 0.463, log-rank test). Of the prognostic indicators used for MBs in the current WHO classification, (2007) the following variables were included into the Cox multivariate survival analysis: patient age, MIB-1 proliferation index, apoptosis index and expression of p53, c-erbB-2 and bcl-2. In addition, the histopathological group (MB vs. supratentorial PNET), CA II, CA IX and CA XII were used in the analysis. These variables were grouped as presented in Table 2. In the Cox analysis, only expression of CA IX (odds ratio 4.31; 95% confidence interval (CI) 1.31 - 14.11; p = 0.016) and the apoptosis index (odds ratio 3.29; 95% CI 1.05 - 10.31, p = 0.041) were independent prognostic factors. The expression of either CA II and CA XII failed to show any significant association with survival.

Bottom Line: Medulloblastomas (MBs) and supratentorial primitive neuroectodermal tumours (PNETs) are the most common highly aggressive paediatric brain 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Tampere University Hospital, Tampere, Finland. kristiina.nordfors@gmail.com

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.

Show MeSH
Related in: MedlinePlus