Histological characterization of T-DM1 induced changes in JIMT-1 xenografts. JIMT-1 xenografts were obtained from mice treated with trastuzumab (A, C, E) or T-DM1 (B, D, F). Histological sections were stained with hematoxylin and eosin (H&E, A, B). HER2 protein was visualized by HercepTest (C-D). Apoptotic cells were visualized by M30 CytoDeath antibody (E-F). High number of cells with aberrant mitotic shape (yellow arrow) and giant multinucleated cells (green arrow), which are the hallmarks of mitotic catastrophe, were seen in T-DM1 treated samples (B, D, F). Furthermore, higher number of apoptotic cells was found in the T-DM1 treated samples than in the trastuzumab treated ones (white arrow, E and F, respectively). Similar number of cells with normal mitotic shape (blue arrow) was found in trastuzumab and T-DM1 treated samples (A). Tumour cells retained their HER2 positivity after long-term trastuzumab (C) or T-DM1 treatment (D), approximately 9 and 15 wks, respectively. HER2 positive intracytoplasmic granules (red arrow) were seen in T-DM1 treated tumours (D), while not in trastuzumab treated ones (C). Giant multinucleated cells were strongly positive for cell membrane HER2 protein (green arrow, D).