The relationship between expression of c-ras, c-erbB-2, nm23, and p53 gene products and development of trophoblastic tumor and their predictive significance for the malignant transformation of complete hydatidiform mole.

OBJECTIVE: The aims of this retrospective study by means of immunohistochemical staining were (1) to study the expression of c-ras, c-erbB-2, p53, and nm23 gene products in complete hydatidiform moles that progress to gestational trophoblastic tumor and in those that remit spontaneously after evacuation, and (2) to estimate the predictive value of the expression of these four gene products in malignant transformation of complete hydatidiform mole.

METHODS: Clinical data of patients with complete hydatidiform mole were obtained by retrospective chart review. Formalin-fixed paraffin sections of 50 cases of complete mole that progressed to gestational tumor and 32 cases of complete mole that remitted spontaneously were studied immunohistochemically for c-ras, c-erbB-2, p53, and nm23 proteins. The prognostic value of the proteins for the malignant transformation of complete mole was analyzed by multiple logistic regression and stepwise logistic estimation. Sections of 30 cases of invasive mole and 19 cases of choriocarcinoma were also immunohistologically studied for expression of the proteins.

RESULTS: Expression of c-erbB-2 and p53 gene products was significantly increased and expression of nm23 and c-ras products was remarkably decreased in complete hydatidiform moles that progressed into postmolar tumor compared with those that remitted spontaneously after evacuation. There was no significant difference in the expression of the four genes in invasive mole and in choriocarcinoma. A logistic estimation model for predicting malignant transformation of complete mole was established based on the expression of gene products. When the expression of four gene products was used, the predictive sensitivity of the regression model was 86.0%, and the specificity was 75.0%. The positive predictive value was 84.3%, the negative predictive value was 77.4%. Logistic stepwise regression analysis showed that the altered expression of c-erbB-2 and nm23 products had strong predictive value, while the expression of c-ras and p53 products had no significant predictive value for the malignant transformation of complete mole.

CONCLUSION: The altered expression of c-ras, c-erbB-2, nm23, and p53 gene products may be important in the pathogenesis of gestational trophoblastic tumor. The decreased expression of nm23 protein and increased expression of c-erbB-2 protein are strong predictors for the malignant transformation of complete mole.