Cancer Res Treat.  2018 Jul;50(3):956-963. 10.4143/crt.2017.181.

Comparison of Clinical Features and Outcomes in Epithelial Ovarian Cancer according to Tumorigenicity in Patient-Derived Xenograft Models

• Eoh KJ
• Chung YS
• Lee SH
• Park SA
• Kim HJ
• Yang W
• Lee IO
• Lee JY
• Cho H
• Chay DB
• Kim S
• Kim SW
• Kim JH
• Kim YT
• Nam EJ

• KMID: 2417884
• DOI: http://doi.org/10.4143/crt.2017.181

Abstract

PURPOSE
Although the use of xenograft models is increasing, few studies have compared the clinical features or outcomes of epithelial ovarian cancer (EOC) patients according to the tumorigenicity of engrafted specimens. The purpose of this study was to evaluate whether tumorigenicity was associated with the clinical features and outcomes of EOC patients.
MATERIALS AND METHODS
Eighty-eight EOC patients who underwent primary or interval debulking surgery from June 2014 to December 2015 were included. Fresh tumor specimens were implanted subcutaneously on each flank of immunodeficient mice. Patient characteristics, progression-free survival (PFS), and germline mutation spectra were compared according to tumorigenicity.
RESULTS
Xenografts were established successfully from 49 of 88 specimens. Tumorigenicity was associated with lymphovascular invasion and there was a propensity to engraft successfully with high-grade tumors. Tumors from patientswho underwent non-optimal (residual disease ≥ 1 cm) primary orinterval debulking surgery had a significantly greater propensity to achieve tumorigenicity than those who received optimal surgery. In addition, patients whose tumors became engrafted seemed to have a shorter PFS and more frequent germline mutations than patients whose tumors failed to engraft. Tumorigenicity was a significant factor for predicting PFS with advanced International Federation of Gynecology and Obstetrics stage and high-grade cancers.
CONCLUSION
sTumorigenicity in a xenograft model was a strong prognostic factor and was associated with more aggressive tumors in EOC patients. Xenograft models can be useful as a preclinical tool to predict prognosis and could be applied to further pharmacologic and genomic studies on personalized treatments.

Keyword

Ovarian neoplasms; Progression-free survival; Patient-derived xenograft

MeSH Terms

Animals
Disease-Free Survival
Germ-Line Mutation
Gynecology
Heterografts*
Humans
Mice
Obstetrics
Ovarian Neoplasms*
Prognosis

Figure

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  Fig. 1. Comparison of progression-free survival in patients relative to the tumorigenicity of engrafted tumors in a xenograft model. (A) Comparison in 88 patients. (B) Subgroup analysis by type of debulking surgery: primary and interval debulking. PDS, primary debulking surgery; IDS, interval debulking surgery.

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  Fig. 2. Comparison of germline mutation spectra relative to tumorigenicity using a 35-multigene panel next-generation sequencing assay. VOUS, variants of unknown significance.

Reference

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