Background. Glioma is the most common and deadly malignancy of the central nervous system. Capillary hemangioblastoma (CHB) is a rare and usually benign tumour of brain, occurring as part von Hippel-Lindau (VHL) disease or as a sporadic entity. For an improved understanding of the molecular mechanisms of the pathogenesis of VHL-related tumours and gliomas, we analysed the expression of the tumour suppressor proteins p53 and p16, and promoter methylation of the tumour suppressor genes (TSGs) MGMT and RASSF1A.
Materials and methods. Expression of p53 and p16 was analysed in 27 cases of glioma, 5 cases of breast cancer, and 17 cases with VHL-related tumours, including CHBs and pheochromocytomas (PCCs), by means of immunohistochemistry. For the gene promoter methylation and deletion assessment, methylation-specific PCR and differential polymerase chain reaction combined with on-chip electrophoresis were used, respectively.
Results. Aberrant expression of the p53 protein was frequent (p < 0.01) in malignant tumours, including gliomas and breast carcinomas, but not in benign tumours (PCC and CHB). Protein p53 alterations were most frequent (65%) in glioblastomas, and a low number (20%) of patients with p53-positive gliomas survived more than one year after diagnosing the disease. Other biomarkers, including loss of p16 expression, promoter hypermethylation of the MGMT gene and promoter hypermethylation or deletion of the RASSF1A gene, were frequent in all groups of tumours.
Conclusions. Alterations of the tumour suppressors p16, MGMT and RASSF1A are frequent in VHL-related tumours, while aberrant expression of p53 is only detectable in malignant tumours – gliomas and breast carcinomas.

Keywords: p53, glioma, capillary hemangioblastoma, pheochromocytoma, breast cancer, promoter methylation