Epithelioid Trophoblastic Tumors: Treatments, Outcomes, and Potential Therapeutic Targets

Abstract

Background: Epithelioid trophoblastic tumors (ETTs) are the rarest type of gestational trophoblastic neoplasias. We investigated the clinical features, treatments, outcomes, and prognostic factors in patients with ETT, and explored potential therapeutic targets.Methods: We retrospectively analyzed the clinical features, treatments, survival, and prognostic factors of 21 ETT patients treated at our institution between January 2002 and December 2017. Expression levels of programmed cell death 1 (PD-1), PD-1 ligands (PD-L1and PD-L2), B7 family ligands (B7-H3, B7-H4, V-domain Ig suppressor of T cell activation [VISTA], and B7-H6), and CD105 expression were assessed by immunohistochemistry.Results: Fourteen patients with ETT (66.7%) presented with irregular vaginal bleeding. Three stage I patients (14.3%) with normal β-human chorionic gonadotropin (β- hCG) levels underwent hysterectomy alone. Of the remaining 18 patients who had elevated β-hCG levels (85.7%), 1 received chemotherapy and 17 underwent surgery and multi-agent chemotherapy. After treatment, 17 patients (81.0%) achieved complete remission (2 of whom [11.8%] later relapsed) and 4 (19.0%) with stage IV died of their disease. On univariate and multivariate analyses, stage IV disease was an independent prognostic factor for overall and disease-free survival (P < 0.001). PD-L1, B7-H3, and CD105 were detected in 100% of samples, PD-L2 and VISTA in 82%, B7-H6 in 18%, and B7-H4 was undetectable in ETT cells.Conclusions: Hysterectomy and metastatic lesion resection are essential for controlling ETT. Surgery plus chemotherapy are recommended for patients with abnormal β-hCG levels and metastatic disease. PD-L1, PD-L2, B7-H3, VISTA and CD105 are potential therapeutic targets for metastatic ETT.

Expression and Significance of Immune Checkpoints in Clear Cell Carcinoma of the Uterine Cervix

“…Expression of PD-L1, B7-H3, B7-H4, and VISTA in CCC of the Cervix. Consistent with our previous study [13,14], the patterns of PD-L1, B7-H3, B7-H4, and VISTA staining in cervical CCC were predominantly membranous; representative images are shown Figure 1. PD-L1 was expressed in both TCs and TAICs and was positive in 11 samples (22%).…”

“…Immunohistochemistry (IHC) was performed using our laboratory protocol as described previously [13,14]. Briefly, 4 μm series of whole tissue sections were deparaffinized and subjected to heat-induced epitope retrieval with 10 mM sodium citrate (pH 6.0) at 95°C for 20 minutes.…”

VISTA expression is associated with a favorable prognosis in patients with high-grade serous ovarian cancer

“…Human tonsil and placenta tissues that were obtained from the Department of Pathology, Peking Union Medical College Hospital, Beijing, China, were used as positive controls, whereas normal tonsil tissues without primary antibodies were used as negative controls. Immunohistochemistry was performed using our laboratory protocol as described previously [13,22].…”

Gestational Trophoblastic Neoplasia, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology

“…The most important prognostic factors include advanced disease stage and interval from last known pregnancy event of $48 months. 124,127,128,134 Additional risk factors associated with less favorable outcomes are advancing age, deep myometrial invasion, tumor necrosis, large tumor size, and mitotic index. 10,128,135 Treatment Approach ITTs are relatively chemoresistant and thus follow a somewhat different treatment paradigm than invasive mole and choriocarcinoma, with surgical intervention playing a more critical role.…”