Evaluation of Clinically Relevant Markers in a Patient-Derived Xenograft Model of Triple-Negative Breast Cancer

Objective: To evaluate a correlation of clinically relevant markers between a patient-derived xenograft (PDX) model and triple-negative breast cancer (TNBC).

Materials and methods: For the PDX model of TNBC, we used tumor tissue from patient E. who presented with right-sided breast cancer at the National Medical Research Centre for Oncology (Rostov-on-Don, Russian Federation). The tumor fragments were subcutaneously implanted into BALB/c nude mice; thus, the first-generation xenograft was obtained. The xenogeneic model was studied on the fourth generation. The PDX model tissues and the patient’s tumor were analyzed by histological, immunohistochemical, and molecular genetic methods. For the immunohistochemical study we used antibodies against ER (estrogen receptor), PR (progesterone receptor), HER2/neu (human epidermal growth factor receptor 2), and Ki-67 (proliferation marker). Molecular genetic testing of the BRCA1 and BRCA2 genes was performed using real-time polymerase chain reaction.

Results: The histological examination demonstrated a correlation between the histotype of the original tumor tissue and the xenograft. Immunohistochemical analysis of the tumor samples revealed no expression of ER, PR, and HER2 markers. We identified 80% of Ki-67-expressing cells in the patient’s tumor and 90% in the xenograft. Furthermore, no mutations in the BRCA1 and BRCA2 genes were found in the patient’s tumor and the corresponding xenograft.

Conclusions: We evaluated clinically relevant markers in the PDX model of TNBC and found the correlation with the corresponding characteristics of the patient’s tumor. Thus, we generated the PDX model that can be utilized for both fundamental and preclinical research in oncology, eg, to study antitumor efficacy of novel drugs in TNBC and identify mechanisms of sensitivity or resistance to various therapeutic interventions.

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