Immunohistochemical and mutational analysis of p53 tumor suppressor gene in gestational trophoblastic disease: correlation with mdm2, proliferation index, and clinicopathologic parameters

The role of p53 in the pathogenesis of gestational trophoblastic disease (G TD) was investigated. Immunohistochemical studies for p53, its regulator md m2, and proliferation marker Ki67 were performed on paraffin-embedded tissu es of 28 partial moles (PM), 57 complete moles (CM), 14 choriocarcinomas (C CA), and 31 normal placentas. Three antibodies to p53 (DO-7, Ab-2, Ab-3) we re used and demonstrated immunoreactivity for wild-type p53 protein predomi nantly in the nuclei of cytotrophoblasts. Direct DNA sequencing of 36 hydat idiform moles using frozen tissues confirmed an absence of mutational chang es in exons 5-8. CCA was found to have the highest p53 protein expression, followed by CM, PM, and normal placenta (P < 0.001). In normal placentas (P = 0.0001), PM, and CM (P = 0.016), an inverse correlation between their ge stational age and p53 expression was observed. p53 expression was found to correlate with proliferation index in normal placenta (P = 0.0001) and all three groups of GTD (P = 0.012). Significant correlation between p53 and md m2 expression was also observed (P < 0.01). The distinctive expression of p 53 wild-type protein in the cytotrophoblasts and its positive correlation w ith the proliferative index suggests that its overexpression in GTD may be related to its effect on cell proliferation. The parallel expression of mdm 2 and p53 also supports the presence of an autoregulatory feedback loop in the control of this process. No correlation could be found between clinical progress of the patients with hydatidiform moles, and the p53 (P = 0.78) o r mdm2 protein (P = 0.54) expression suggesting that neither of them carrie s any prognostic significance.