p21(WAF1/CIP1) expression in gestational trophoblastic disease: correlation with clinicopathological parameters, and Ki67 and p53 gene expression

Abstract

Background--The p21(WAF1/CIP1) gene mediates growth arrest by inhibiting G 1 cyclin dependent kinases and has been considered as a downstream effector of the tumour suppressor gene p53. Aim--To analyse the role of p21(WAF1/CIP1) in gestational trophoblastic disease. Methods--The immunohistochemical expression of p21(WAF1/CIP1) gene was measured in 33 placentas, 28 partial hydatidiform moles, 54 complete hydatidiform moles, and 13 choriocarcinomas in paraffin wax embedded tissue. The results were correlated with p53 (DO7) and Ki67 (MIB1) immunoreactivity as well as clinical progress. Results--p21(WAF1/CIP1) immunoreactivity was found predominantly in the nuclei of the syncytiotrophoblasts. p21(WAF1/CIP1) protein expression correlated with gestational age in normal placentas (p = 0.0001) but not in hydatidiform moles (p = 0.89). Complete hydatidiform moles and choriocarcinomas had a significantly higher p21(WAF1/CIP1) expression compared with normal placentas and partial hydatiform moles (p < 0.001); there was no difference between placentas and partial hydatidiform moles. No correlation between p21(WAF1/CIP1) expression and either the proliferation (Ki67) index (p = 0.34) or p53 protein accumulation (p = 0.68) was demonstrated. There was no significant difference (p > 0.05) in p21(WAF1/CIP1) expression between the 17 patients who developed persistent gestational trophoblastic disease and those who did not. Conclusions--This study suggests that p21(WAF1/CIP1) expression in trophoblastic disease may be induced by a p53 independent pathway. The proliferative activity of gestational trophoblastic diseases might not be determined solely by the control of the cell cycle operated by p21(WAF1/CIP1). p21(WAF1/CIP1) expression is not an accurate prognostic indicator of gestational trophoblastic disease.