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Establishment of Patient-Derived Tumor Xenograft Models of High-Risk Endometrial Cancer

Zhu, Menghan, MD*†; Jia, Nan, MD*†; Nie, Yanyan, MS‡§; Chen, Jun, PhD; Jiang, Yahui, MD*†; Lv, Tianjiao, MD, PhD*†; Li, Yuanyuan, PhD‡§; Yao, Liangqing, MD, PhD*†; Feng, Weiwei, MD, PhD

International Journal of Gynecological Cancer: November 2018 - Volume 28 - Issue 9 - p 1812–1820
doi: 10.1097/IGC.0000000000001365
Basic Science

Objective High-risk endometrial cancers (ECs), including high-grade EC, serous carcinoma (SC), clear cell carcinoma, and carcinosarcoma, account for 50% of deaths due to ECs. Therapies for these cancers are limited, and patient-derived tumor xenograft (PDTX) models are useful tools for preclinical drug evaluation, biomarker identification, and personalized medicine strategies. Here, we used and compared 2 methods to establish PDTX models.

Methods Fresh tumor tissues collected from 18 primary high-risk EC patients (10 high-grade ECs, 6 SCs, 1 clear cell carcinoma, and 1 carcinosarcoma) were engrafted subcutaneously and in the subrenal capsule in NOD/SCID for establishment and Balb/c-nu/nu mice for expansion. Histology and cytokeratin, estrogen receptor, progesterone receptor, and P53 expression were evaluated to assess the similarity of primary tumors and different generations of PDTX tumors. Whole-exome sequencing (WES) and RNA sequencing were used in 2 high-grade EC models to verify whether the genetic mutation profiles and gene expression were similar between primary and PDTX tumors.

Results The total tumor engraftment rate was 77.8% (14/18) regardless of the engraft method. The tumor engraftment rate was increased in subrenal capsule models compared with subcutaneous models (62.5% vs 50%, P = 0.464). The time to tumor formation varied significantly from 2 to 11 weeks. After subrenal capsular grafting, grafted tumors could be successfully transplanted to subcutaneous sites. We observed good similarity between primary tumors and corresponding different passages of xenografts.

Conclusions The combination of 2 engrafting methods increases the tumor engraftment rate. The high tumor engraftment rate ensures the establishment of a high-risk EC biobank, which is a powerful resource for performing preclinical drug-sensitivity tests and identifying biomarkers for response or resistance.

*Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University;

Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases;

Shanghai Center for Bioinformation Technology;

§Shanghai Engineering Research Center of Pharmaceutical Translation;

Shanghai Gemple Biotechnology Co Ltd; and

Department of Gynecology and Obstetrics, School of Medicine, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, China.

Address correspondence and reprint requests to Weiwei Feng, MD, PhD, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Ruijin 2nd Rd 197, Shanghai, 200025, China. E-mail: fww12066@rjh.com.cn; or to Liangqing Yao, MD, PhD, Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shenyang Rd 128, Shanghai, 200090, China. E-mail: yaoliangqing@163.com.

This work was supported by grants to W.F. from the Shanghai Science and Technology Committee (STCSM) (no. 15140903200 and 16411953500) and the National Natural Science Foundation of China (no. 81572836).

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.ijgc.net).

Received June 2, 2018

Received in revised form July 19, 2018

Accepted August 26, 2018

© 2018 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.