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

Abstract

PurposeAlthough 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 MethodsEighty-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.ResultsXenografts 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.ConclusionsTumorigenicity 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.

Biliary tract cancer patient-derived xenografts: Surgeon impact on individualized medicine

“…22 Similar results have been described for a variety of tumor types, including colorectal cancer, breast cancer, and ovarian cancer. [37][38][39] Our study had similar findings with significant reductions in recurrence free survival for patients with successful PDX models. This positive correlation presents an opportunity to identify patients who are at a high risk for recurrence following their resection and also an opportunity to utilize the derived PDX tumors to identify potential therapies for clinical use prior to documented clinical recurrence.…”

Establishment of patient‐derived xenograft model in ovarian cancer and its influence factors analysis

“…Certainly, there was still controversial about the relationship between tumor type and TFR of PDX models. Previous studies reported that the TFR of PDX models in high‐grade serous ovarian cancer was higher than low‐grade serous ovarian cancer . While another author insisted that there was no relationship between tumor type and TFR of PDX models, so the relationship between tumor type and TFR of PDX models still needed larger sample size to verify.…”

“…Previous studies reported that the TFR of PDX models in high-grade serous ovarian cancer was higher than low-grade serous ovarian cancer. 15,31 While another author insisted that there was no relationship between tumor type and TFR of PDX models, 18 so the relationship between tumor type and TFR of PDX models still needed larger sample size to verify. In addition, previous studies have reported that the immunodeficient degree of experimental animals, the location of tumor derived, and the transplanted location of cancer were another important factors for TFR of PDX models.…”

Ovarian Cancers: Genetic Abnormalities, Tumor Heterogeneity and Progression, Clonal Evolution and Cancer Stem Cells

“…This finding was systematically observed in all studies and offered the opportunity to evaluate a possible link between tumor growth in xenotransplantation assay and biological properties of ovarian cancers. Thus, two recent studies based on xenotransplantation of patient’s derived fresh ovarian tumor tissues xenografted either subcutaneously or in the subrenal capsule showed that patients whose tumors became engrafted have reduced progression survival and overall survival, compared to patients whose tumors failed to engraft [ 322 , 323 ]. These observations suggest that xenograft models can be useful as a preclinical tool to predict prognosis.…”