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Open Access Research article

VRK2 identifies a subgroup of primary high-grade astrocytomas with a better prognosis

Irene Rodríguez-Hernández123, Marta Vázquez-Cedeira12, Angel Santos-Briz34, Juan L García1, Isabel F Fernández13, Juan A Gómez-Moreta5, Javier Martin-Vallejo6, Rogelio González-Sarmiento123* and Pedro A Lazo12*

Author Affiliations

1 Instituto de Biología Molecular y Celular del Cáncer, CSIC-Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain

2 Instituto de Investigación Biomédica de Salamanca-IBSAL, Hospital Universitario de Salamanca, Salamanca, Spain

3 Unidad de Medicina Molecular, Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain

4 Departamento de Patología, Hospital Universitario de Salamanca, Salamanca, Spain

5 Departamento de Neurocirugía, Hospital Universitario de Salamanca, Salamanca, Spain

6 Departamento de Estadística, Universidad de Salamanca, Salamanca, Spain

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BMC Clinical Pathology 2013, 13:23  doi:10.1186/1472-6890-13-23

Published: 1 October 2013

Abstract

Background

Malignant astrocytomas are the most common primary brain tumors and one of the most lethal among human cancers despite optimal treatment. Therefore, the characterization of molecular alterations underlying the aggressive behavior of these tumors and the identification of new markers are thus an important step towards a better patient stratification and management.

Methods and results

VRK1 and VRK2 (Vaccinia-related kinase-1, -2) expression, as well as proliferation markers, were determined in a tissue microarray containing 105 primary astrocytoma biopsies. Kaplan Meier and Cox models were used to find clinical and/or molecular parameters related to overall survival. The effects of VRK protein levels on proliferation were determined in astrocytoma cell lines. High levels of both protein kinases, VRK1 or VRK2, correlated with proliferation markers, p63 or ki67. There was no correlation with p53, reflecting the disruption of the VRK-p53-DRAM autoregulatory loop as a consequence of p53 mutations. High VRK2 protein levels identified a subgroup of astrocytomas that had a significant improvement in survival. The potential effect of VRK2 was studied by analyzing the growth characteristics of astrocytoma cell lines with different EGFR/VRK2 protein ratios.

Conclusion

High levels of VRK2 resulted in a lower growth rate suggesting these cells are more indolent. In high-grade astrocytomas, VRK2 expression constitutes a good prognostic marker for patient survival.

Keywords:
Astrocytoma; Glioblastoma; VRK1; VRK2; Immunohistochemistry; Prognosis