Does p53 expression correlate with p21 expression in cancer of the uterine corpus?
Until recently, it was generally assumed that p53 expression equated with tp53 mutation in cancers of the uterine corpus. Skomedal et al., [1] have demonstrated that there was no correlation between p53 expression and point mutation in exons 5ยฑ8 of tp53. This supports our observation that tp53 mutations could not be found in any of 18 endometrioid endometrial carcinomas known to overexpress p53 protein [2].
Skomedal et al. observed p21 overexpression in 36% of their cases and regard this as a surprisingly high frequency, as p21 expression is expected to suppress cell growth. However, it has been shown by Yaginuma et al.
[3] that p21 expression is age-dependent (increasing in post-menopausal women). Several groups have found p21 expression in up to 62% of endometrial cancers [4,5]. In a sample of 16 endometrioid endometrial cancers from post-menopausal women (mean age 70.6 years), we observed p21 overexpression in 62.5% of cases [6]. Skomedal et al. do not state the ages of their patients.
Skomedal et al. have attempted to evaluate the accumulation of p21 and p53 proteins semiquantitatively and were unable to demonstrate a signiยฎcant correlation between p53 expression and p21 expression. Using a quantitative assessment of immunoreactivity, we were also unable to show a correlation between p53 overexpression and p21 expression. We also failed to demonstrate a correlation between p53 expression and apoptosis, or between p21 and apoptosis. Our data suggest, however, that p21 expression occurs with very low levels (1ยฑ6%) of wildtype p53 activity [6]; this relationship was not explored by Skomedal et al. This would be expected if p21 expression is a downstream effect of p53-induced apoptosis. It may be that, in the absence of tp53 mutation, the presence of high p53 levels without prominent apoptosis represents an alternative mechanism to mutation causing abnormal stabilization of the p53 protein. The biological relationship between p53 expression and p21 expression remains uncertain in endometrial carcinoma and a larger study is needed.