Gestational trophoblastic diseases (GTD) include benign conditions (e.g., tumor-like lesions, abnormal non-molar villous lesions), pre-malignant conditions (e.g., complete or partial hydatidiform moles), and gestational trophoblastic neoplasia (GTN) [1]. The latter includes invasive moles, choriocarcinomas, placental site trophoblastic tumors (PSTT) and epithelioid trophoblastic tumors (ETT).

GTN arises from a pregnancy event and is morphologically characterized by the presence of trophoblast cells, and biologically by the production of human chorionic gonadotropin (hCG). Non-gestational solid tumors may also present with choriocarcinomatous differentiation and produce hCG, such as poorly differentiated carcinomas [2]. hCG-producing carcinomas originating from the bladder [3], cervix [4], pancreas [5] and other sites (including lung and endometrium) have been described [6]. While the 5-year overall survival of patients with GTN is generally greater than 90%, the prognosis of patients with non-gestational hCG-producing tumors is variable and depends primarily on the type of primitive tumor [7].

To appropriately tailor treatment to the tumor type, it is crucial to determine whether hCG-producing tumors have a gestational or non-gestational origin. In addition, for patients with GTN the nature of the causal pregnancy and the interval since its termination are required to calculate the FIGO risk score to determine the required treatment strategy. Low-risk GTN is defined by a FIGO score ≤6 where treatment generally consists of single agent chemotherapy; hysterectomy may also be offered if there is no radiologic evidence of metastatic disease. Patients with a FIGO score ≥7 require multi-agent chemotherapy [1].

Molecular DNA genotyping is an ancillary technique using Polymerase Chain Reaction (PCR) to analyze short-tandem repeat (STR) polymorphisms. This can be used to classify hydatidiform moles (i.e., complete vs. partial mole) according to the number of paternal and/or maternal alleles [8]. Molecular genotyping can also be used to to distinguish GTN from non-gestational trophoblastic tumors of germ-cell or somatic origin, since paternal alleles are present only in the former [8].

The primary objective of this study is to describe the cohort of patients with hCG-producing tumors from the French Reference Center for Trophoblastic Diseases (FRCTD) and assesses the impact of molecular genotyping on diagnosis and therapeutic management.. The secondary objective is to assess patient prognosis and overall survival based on gestational vs. non-gestational tumor origin.