Circulating Tumor DNA: A Potential Novel Diagnostic Approach in Gestational Trophoblastic Neoplasia.

http://dx.doi.org/10.1016/j.ebiom.2016.01.013 2352-3964/Crown Copyright © 2016 Published by Elsevie Gestational trophoblastic diseases (GTD) are a group of disorders that originate from the trophoblast, which is the outer layer of the blastocyst that normally gives rise to the placenta and is the first tissue to differentiate from the developing embryos after implantation. The human chorionic gonadotropin (hCG) is one of the pregnancy hormones and is secreted by trophoblastic cells. hCG is detected in maternal blood seven days after fertilization (Cole, 2009) and is an excellentmarker to detect chemical, normal and abnormal pregnancies. GTD include pre-malignant stages, partial and complete hydatidiform moles, and gestational trophoblastic neoplasia (GTN), which encompass invasive mole, choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor, and are all characterized by excessive proliferation of the trophoblast and therefore excessive production of hCG. Among GTD, hydatidiform mole is the most common. After initial diagnosis by ultrasound and serum hCG quantitation, hydatidiformmoles are removed by dilatation and curettage suction and the patients are followed-up with serial hCG measurements until negativity or non-pregnant levels. Abnormal decrease of hCG after curettage indicates risk of persistent trophoblastic disease and malignant transformation into GTN (Fig. 1) that are classified and treated according to the International Federation of Gynecology and Obstetrics (FIGO) guidelines (FIGO Oncology Committee, 2002; Seckl et al., 2010). The implementation of these guidelines has contributed to a better management of GTD and changed their outcomes from nearly 100% fatality 60 years ago (Goldstein, 2012) to nearly 100% cure rates in current clinical practice (Bolze et al., 2015). However, some patients still present with advanced or chemoresistant GTN. In addition, hCG is a common tumor marker that is expressed by germ cell tumors of the testis and the ovary and by 20–40% of common epithelial carcinoma such as bladder, cervix, lung, and naso-pharynx (Iles, 2007).Many of these tumors are not 100% curable and those that express hCG have the lowest survival rate. In this issue of EBioMedicine, Openshaw et al. (2016) looked for circulating free DNA (cfDNA) in the plasma of 18 women with postmolar GTN, two with metastatic gestational choriocarcinoma, and five