Translation of triple-negative breast cancer behavior from the xenograft model to human model

Background: for xenograft models of triple-negative breast cancer (tnbc) to be valuable in the development of molecularly-targeted drugs, careful characterization is essential to their validation. the present study aimed to validate the tnbc xenograft model with a specific focus on angiogenesis. methods: twelve tnbc xenograft tumors and 12 human breast cancer tumors (htnbcs) were included in this study. both groups were grade iii and p53- positive. nuclear pleomorphism and mitotic count were analyzed by hematoxylin and eosin (h&e) stains respectively. basal cytokeratin (ck5/6), vimentin, cathepsin-d, ki-67 (for proliferation), and mvd-cd34 (for angiogenesis) markers were examined by immunohistochemistry (ihc). the association of mmicrovesseles density (mvd) with ki-67, nuclear pleomorphism, and mitotic count was assessed in each group separately, and htnbcs were compared with the xenograft group. results: the xenograft models showed a significant correlation between angiogenesis (mvd) and cell proliferation (ki-67), nuclear pleomorphism, and mitotic count (p= 0.0398; p= 0.020; p=0.001, respectively). the htnbc group also showed a similar trend, except for nuclear pleomorphism (p=0.193), which did not correlate with angiogenesis. comparison between the two groups showed significant changes in cell proliferation (ki-67 and vimentin). the difference in proliferation rate and vimentin expression between the two groups can be due to the biological diversity between human and mice and epithelial-mesenchymal transition (emt), respectively. conclusion: our results, re-emphasize the significance of angiogenic treatment therapy in patients with tnbc, and further validate the tnbc xenograft model as a valid model for drug discovery and development.