Expression patterns of maspin and mutant p53 are associated with the development of gestational trophoblastic neoplasia.

Abstract

Gestational trophoblastic disease (GTD) is a group of conditions that originate from the abnormal proliferation of trophoblastic cells. GTDs encompass hydatidiform moles (HMs) and gestational trophoblastic neoplasia (GTN). GTNs are a group of malignant diseases that require chemotherapy, or more aggressive treatment. There is a requirement for more tumor markers to predict the development of GTN from HMs. The current study evaluated the expression of maspin and tumor protein p53 (p53) in GTD, and their role in predicting the development of GTN. Expression of maspin and mutant p53 (m-p53) was detected by immunohistochemistry in 48 normal first trimester placentas, matched for gestational age to 49 HMs that regressed, 39 malignant HMs and 11 invasive moles or choriocarcinomas. Spearman's rank correlation analysis and logistic regression were performed on the expression patterns of maspin and m-p53, and on the clinical prognostic factors in GTD. Compared with normal placenta levels, the expression levels of maspin were decreased, whereas the expression levels of m-p53 were increased in GTDs (P<0.05). The expression levels of maspin and m-p53 in complete and partial HMs were not significantly different (P>0.05). In HMs, maspin expression was inversely correlated with serum β human chorionic gonadotropin, uterine size and diameter of theca-lutein cysts; however, m-p53 expression demonstrated a positive correlation with these factors (all P<0.05). Compared with the high-risk metastatic group (FIGO score ≥7), the low-risk group (FIGO score <7) exhibited a higher rate of positive maspin expression (P=0.041), and the frequency of positive m-p53 expression was significantly higher in patients with an advanced FIGO stages (FIGO stage ≥III) compared with patients in early stages (FIGO stage ≤II; 87.9 vs. 58.8%; P=0.019). The combination of maspin negative expression with m-p53 positive expression had an 84% specificity value, 76% positive predictive value and 70% negative predictive value for the development of GTN. In conclusion, maspin-negative and m-p53-positive expression is associated with the development of GTN in HMs.