Purpose: Both negative and positive influences of mutant p53 on treatment outcome have been reported, and we present here a meta-analysis of published studies where outcome was reported for defined treatment groups.
Methods: We identified articles on the effect of p53 status by treatment modality, excluding those not stratified by method of treatment. A common hazard ratio was estimated from studies that reported a multivariate analysis. We also estimated the numbers of patients expressing the endpoint at the mean or median follow-up time and calculated a pooled odds ratio.
Results: Twenty-eight articles were evaluable (23 using immunohistochemistry to detect overexpression of p53 and 8 using DNA sequencing), for a total of 4,416 patients. For patients treated with surgery only, the immunohistochemistry studies showed a significant influence of p53 status on disease-free survival and a marginally significant influence on overall survival. In the studies using DNA sequencing, by contrast, there was a significant influence of p53 mutations on overall survival, but not disease-free survival. For patients treated with surgery and radiotherapy, the influence of p53 status on disease-free survival was either insignificant or marginally significant, depending on test used; there was no influence on overall survival.
Conclusions: Although this pooled analysis of published studies where treatment was accounted for shows that there is a borderline significant hazard associated with p53 overexpression or mutation vs. p53 wild-type, it is unlikely that p53 can be applied in a routine clinical setting alongside factors such as T stage, nodal status, and residual tumor, whose prognostic value is much stronger.