Figure 5

T-DM1 induced mitotic catastrophe and apoptosis in JIMT-1 xenografts. For histology, JIMT-1 tumours were obtained from SCID mice treated with control antibody (rituximab, black column), lapatinib (gray column), trastuzumab (white column), T-DM1 (hatched column) or T-DM1 after trastuzumab (cross-hatched column). Histological sections were stained with hematoxylin and eosin. When enumerating the number of mitoses with normal morphology, no differences were found between the samples (A). In contrast, a significantly higher number of cells with aberrant mitotic morphology was detected in T-DM1 treated tumours (B) (*, P < 0.05). The number of giant multinucleated cells was also increased in T-DM1 treated samples (C) (*, P < 0.05). Notably, higher number of cells with aberrant mitotic morphology and higher number of giant multinucleated cells were detected in the samples whose trastuzumab treatment was changed to T-DM1 (B-C) (*, P < 0.05). CytoDeath staining was used to detect the apoptotic cells in the histological sections. Significantly increased number of apoptotic cells was found in the T-DM1 treated samples and also in the in the samples whose trastuzumab treatment were changed to T-DM1 (D) (*, P < 0.05). Note that CytoDeath positive cells are plotted on different scales.