p53, p21, Rb and mdm2 oncoproteins: Expression in normal placenta, partial and complete mole, and choriocarcinoma

OBJECTIVE: To determine the expression of p53, p21, Rb and mdm2 proteins in normal placentas, partial and complete hydatidiform moles, and choriocarcinomas and to examine possible p53 mutations in specimens from p53- positive cases. STUDY DESIGN: Expression of the above oncoproteins was determined immunohistochemically by specific antibodies for these proteins on formalin-fixed paraffin sections of 18 normal placentas, 17 partial moles, 25 complete moles and 11 choriocarcinomas. This was followed by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis (exons 5, 6, 7, 8, 9, 10, 11) for possible p53 mutation in specimens from p53- positive cases of complete mole and choriocarcinoma. RESULTS: p53 Oncoprotein immunoreactivity was significantly stronger in complete mole and choriocarcinoma than in normal placenta (P <.0001, P <. 0001) and in partial mole (P < .0001, P <. 0001). Positive staining for p21 oncoprotein was also significantly stronger in complete mole (P < .0001, P <. 0001) and in choriocarcinoma (P < .0001, P <. 0001) than in placenta and partial mole. We found significantly stronger staining for Rb protein in complete mole (P < .03) and choriocarcinoma (P < .03) than in partial mole. Partial mole and complete mole expressed significantly stronger staining of mdm2 than placenta (P < .007, P < .07, respectively). We found only one nonsense mutation in p53 with PCR analysis; that strongly suggests that in complete mole and choriocarcinoma the overexpressed p53 protein was wild type. CONCLUSION: Altered expression of p53, p21, Rb and mdm2 may be important in the pathogenesis of both complete mole and choriocarcinoma. However, unlike complete molar pregnancy, partial mole is not characterized by overexpression of p53. Overexpression of p53 and mdm2 proteins in complete mole and choriocarcinoma may be associated with more aggressive behavior in gestational trophoblastic disease.