Immunohistochemical Evaluation of Tumor Characteristic Retention in Triple-negative Breast Cancer PDOX Models

Patient-derived xenograft (PDX) and Patient-derived orthotopic xenograft (PDOX) models are considered to recapitulate the heterogeneity and biological characteristics of original tumors more faithfully than conventional models. This study aimed to evaluate the extent to which specific tumor markers are retained in PDOX models of triple-negative breast cancer (TNBC), in comparison with their corresponding patient tumors.

PDOX models were established by orthotopically implanting tumor tissues from 15 TNBC patients into the mammary fat pads of immunodeficient mice. Immunohistochemical analyses were performed for CK5/6, HER2, EGFR, androgen receptor (AR), and Trop-2 in both the patient tumors and their corresponding PDOX tissues to evaluate the concordance of molecular marker expression.

Trop-2 expression was consistently preserved across all tumor PDOX models. EGFR expression was preserved. In contrast, AR expression was observed in two of the original tumors, but it was completely lost in the corresponding PDOX models. CK5/6 and HER2 showed variable preservation.

TNBC PDOX models are promising tools for preclinical drug evaluation; however, variability in the retention of molecular targets, such as AR, CK5/6, and HER2, emphasizes the importance of verifying marker expression prior to functional analysis. Tumor heterogeneity and clonal selection during engraftment may contribute to these discrepancies.