Relationship between alterations in the p53 tumor suppressor gene and prognosis of ovarian cancer
Mutation and overexpression of the p53 tumor suppressor gene are the most frequently described genetic alterations noted thus far in epithelial ovarian cancers; and it is thought that loss of p53 tumor suppressor function plays a significant role in the pathogenesis of these cancers. Most cancers that overexpress p53 protein have been found to contain missense mutations in the DNA binding regions of the gene in exons 5-8, but some cancers with truncation mutations or that lack mutations also express immunohistochemically detectable p53. There is a consensus in the literature that p53 overexpression is much more common in advanced-stage ovarian cancers (40-60%) relative to early-stage cases that are confined to the ovaries (15%). Some, but not all, studies have suggested that p53 overexpression in stage III-IV disease is associated with about 10-20% worse 5-year survival. None of the studies reported thus far has included both immunostaining and mutational analysis of p53 in cohorts of patients receiving standardized treatment, however. Until such studies are performed the prognostic significance of mutation and overexpression of p53 in ovarian cancer will remain somewhat uncertain.