Discovery of the prognostic marker in the whole blood sample of gestational trophoblastic neoplasia beyond immunohistochemical tissue markers: mdm2

Abstract

Gestational trophoblastic disease (GTD) is an abnormal trophoblastic proliferation disease that may show malignant progression. Despite reports on the clinical and laboratory parameters for the projection of GTD, there is still a lack of histopathologic or genetic prognostic markers for patients with higher risks of malignant progression and high-risk gestational trophoblastic neoplasia. The primary aim of this study was to identify a marker other than tissue markers for evaluating the progression potential of GTD to gestational trophoblastic neoplasia (GTN). The secondary aim was to determine the tissue marker capacity to detect the progression to neoplasia. The study design was a case-control. The data of 81 patients diagnosed with GTD and 23 control were assessed. Their detailed obstetric and gynecological history were recorded, and their whole blood sample was obtained for genetic evaluation of the mouse double minute 2 (mdm2) gene expression. We also evaluated the curettage specimens for p53, c-erythroblastic oncogene B-2 (c-erbB-2), and ki67 protein expression. The expression of p53 expression was significantly increased in GTD patients and significantly higher in the GTN progressing group than in the spontaneous remission group. Although blood mdm2 gene was significantly different between the low and high-risk GTN subgroups, its expression was not different between the GTD or GTN groups. Additionally, a significant increase in c-erbB-2 was observed in the GTN group. Mdm2 might be a promising blood prognostic factor throughout the course of GTD. p53 and c-erbB-2 might be used as predictive indicators for the early diagnosis of GTN progression. Altogether, these markers may help identify patients with high risks of malignant progression, guide earlier aggressive treatment and increase treatment outcomes.