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 protei ns in and complete hydatidiform moles, and choriocarcinomas and to exa mine possible p53 mutations in specimens from p53-positive cases. STUD Y DESIGN: Expression of the above oncoproteins Teas determined immunoh is tochemically by specific antibodies for these proteins on formalin- fixed paraffin sections of 18 normal placentas, 17 partial moles, 25 c omplete moles and 11 choriocarcinomas. This was followed by polymerase chain reaction single-strand conformation polymorphism (PCX-SSCP) ana lysis (exons 5, 6, 7, 8, 9, 10, 11) for possible p53 mutation in speci mens from p53-positive cases of complete mole and choriocarcinoma. RES ULTS: p53 Oncoprotein immunoreactivity was significantly stronger in c omplete mole and choriocarcinoma than in normal placenta (P < .0001, P < .0001) and in partial mole (P < .0001, P < .0001). Positive stainin g 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 sta ining 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 PC R analysis; that strongly suggests that in complete mole and choriocar cinoma the were expressed p53 protein was wild type. CONCLUSION: Alter ed expression of p53, p21, Rb and mdm2 may be important in the pathoge nesis of both complete mole and choriocarcinoma. However, unlike compl ete molar pregnancy, partial mole is not characterized by overexpressi on of p53. Overexpression of p53 and mdm2 proteins in complete mole an d choriocarcinoma may be associated with more aggressive behavior in g estational trophoblastic disease.