Abstract C13: Patient derived gastric carcinoma xenograft (PDGCX) models largely maintain the histological and genetic diversities of corresponding patient tumor.

Abstract

Abstract Purpose: To assess molecular characteristic of patient derived gastric cancer xenograft (PDGCX) models for evaluating whether these models maintain corresponding patients’ histological and genetic diversities. Experimental procedures: Patient derived gastric carcinoma xenograft models were established by implanting subcutaneously GC patients’ tumor tissue from non-necrotic areas into immune-deficient mice (nude mice or SCID mice). Formalin-fixed paraffin embedded (FFPE) sections of each model and corresponding patient tumor tissue were prepared for characterization studies. Histological features were assessed by pathologist on H&E stained slides. To profile several cancer relevant markers such as ERBB1, ERBB2, ERBB3, FGFR2, MET and PTEN, multilayered biological assays were performed including gene copy number by fluorescent in situ hybridization (FISH) and/or protein expression by immnuohistochemistry (IHC). Results: Twenty patient derived GC xenograft models were established with a take on rate of 17%. These models retained the histological features of their parental tumors. No statistical significance was observed between the successful cases and failed cases in terms of patients’ clinical parameters including age, gender, tumor grade, Lauren type and clinical stage. Gene copy number and/or protein expression of gastric cancer relevant biomarkers such as ERBB1, ERBB2, ERBB3, FGFR2, MET and PTEN were detected by FISH and/or IHC. Among 20 established models, 100% (20/20) were ERBB1 highly expressed, 20%(4/20) were ERBB2 positive, 90% (18/20) were ERBB3 highly expressed, 10% (2/20) harbored FGFR2 amplification, 45% (9/20) lost PTEN expression and 15% (3/20) were defined as MET amplification. This prevalence was comparable with the incidences of these biomarkers in human. High degree of similarity was observed in DNA level for ERBB2, FGFR2 and MET genes between PDGCX model and corresponding primary tumor (k=1). Expression of ERBB2, ERBB3 and PTEN defined by IHC also showed substantial or perfect agreement between PDGCX and their parent tumor (k=0.615∼1), while ERBB1 expression showed slight agreement (k=0). Genetic characteristics between the parent tumor and subsequent passages of the PDGCX were also largely retained. The ERBB2 positive, FGFR2 or MET amplification were recapitulated until passage12. Conclusion: 20 patient derived gastric carcinoma xenograft models were established with 17% engraft rate. The histological assessment and several gastric oncogenic biomarkers’ profiling data demonstrated that these patient derived GC models well represent GC diversity. Furthermore, the stability of the molecular profile across the different passages of individual models showed translational significance that these models could serve for in vivo testing of personalized therapies. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C13. Citation Format: Xinying Su, Tianwei Zhang, Lin Zhang, Yanping Xu, Shuqiong Fan, Yuan Jie Liu, Meizhuo Zhang, Hao Chen, Liang Xie, Jingchuan Zhang, Xiaolu Yin, Yi Gu, Xingzhi Ni. Patient derived gastric carcinoma xenograft (PDGCX) models largely maintain the histological and genetic diversities of corresponding patient tumor. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C13.