Histologic and molecular analysis of patient derived xenografts of high-grade serous ovarian carcinoma

Ruifen Dong, Wenan Qiang, Haiyang Guo, Xiaofei Xu, J. Julie Kim, Andrew Mazar, Beihua Kong*, Jian Jun Wei

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Background: Patient derived xenografts (PDX) are generated by transplanting the original patient's tumor tissue into immune-deficient mice. Unlike xenograft models derived from cell lines, PDX models can better preserve the histopathology from the original patient and molecular pathways. High-grade serous carcinoma (HGSC) is a deadly form of ovarian/fallopian tube cancer whose response to current chemotherapies varies widely due to patient variability. Therefore, a PDX model can provide a valuable tool to study and test treatment options for each individual patient. Methods: In this study, over 200 PDX tumors from nine HGSC were analyzed to investigate the nature and behavior of PDX tumors originating from HGSC. PDX tumors were serially passaged (from P0 to P4) and tumors were grafted orthotopically under the ovarian bursa or subcutaneously. Results: Comparative analysis of the histology and molecular markers of tumors from over 200 PDX tumor-bearing mice, revealed that the tumors maintained similar histologies, stem cell populations, and expression for the majority of the tested oncogenic markers, compared to the primary tumors. However, a significant loss of steroid hormone receptors and altered expression of immunoresponsive genes in PDX tumors were also noted. Conclusion: Our findings provide substantial new information about PDX tumor characteristics from HGSC which will be valuable towards the development of personalized therapy and new drug development for HGSC.

Original languageEnglish (US)
Article number92
JournalJournal of Hematology and Oncology
Volume9
Issue number1
DOIs
StatePublished - Sep 21 2016

Keywords

  • High-grade serous carcinoma
  • Immunohistochemistry
  • Intrabursal engraft histology
  • Patient-derived xenograft

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Oncology
  • Cancer Research

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