The challenge of p53 as prognostic and predictive factor in gliomas

Abstract

In recent years, increasing interest in genetic abnormalities and biologic factors such as the tumour suppressor gene p53 as possible predictive and prognostic factor in gliomas has emerged. Inactivation of p53 can result in resistance to apoptosis, one of the mechanisms thought to explain the failure to respond to DNA-damaging agents. Thus, inactivation of p53 might be associated with a worse prognosis. Considering the inconsistent results of several recent studies, it has remained controversial whether p53 actually can be related to response to treatment and patients' prognosis. Therefore, a systematic review of the literature was performed, which included 28 publications. Techniques for assessing the inactivation of p53 varied widely. Overall, approximately 50% or more of astrocytoma specimens evaluated by immunohistochemistry stained positively for p53, regardless of histologic grade. Eight studies were restricted to comparably treated patients within a single histologic group. In most instances, non-restrictive inclusion criteria and use of statistical methods, which were not sufficient to correct the possible bias, make it difficult to reach unequivocal conclusions. However, it appears that the prognostic information of p53 is at best marginal, especially when compared to established parameters such as grading, age, etc. Its predictive value, which most likely is rather limited too, can hardly be judged without prospective studies also evaluating other biological factors as well as end-points other than time to radiological progression.