J Cancer 2019; 10(1):11-19. doi:10.7150/jca.28134

Research Paper

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

Junjun Yang1*, Liju Zong1*, Jing Wang2, Xirun Wan 1, Fengzhi Feng 1, Yang Xiang 1✉

1. Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, PR China.
2. Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, PR China.
*These authors contributed equally to this work.

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.

Keywords: epithelioid trophoblastic tumor, prognosis, surgery, immune checkpoint

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Yang J, Zong L, Wang J, Wan X, Feng F, Xiang Y. Epithelioid Trophoblastic Tumors: Treatments, Outcomes, and Potential Therapeutic Targets. J Cancer 2019; 10(1):11-19. doi:10.7150/jca.28134. Available from http://www.jcancer.org/v10p0011.htm