Histopathological findings in mice receiving esVEGFR-2 gene therapy. The implanted mammary carcinomas proved to be moderately differentiated adenocarcinoma (A-C, scale bar = 50 μm). Histopathologically, no apparent differences in mammary carcinomas were found between the pVec (A) and pesVEGFR-2 (B) groups. However, mammary carcinomas in the pEndo group showed spoke-like cell death regions (asterisks) within viable tumor cells (C). The cell death region was observed around blood vessels (asterisk) and apoptotic bodies (arrows) were seen along with the cell death area (C). p53 immunohistochemistry of mammary carcinoma induced by BJMC3879luc2 cell inoculation (D, scale bar = 25 μm). Note nuclear staining for abnormal p53 protein, indicating that these cells carry mutant p53. Metastasis to lymph node in the pVec (E), pesVEGFR-2 (F) and pEndo (G) (E-G, scale bar = 50 μm). Metastatic carcinoma cells were presented in medullary cord and intraluminal space of the blood vessel (E, arrows). Metastatic carcinoma cells were filled with subcapsular sinus (asterisk) and cortical sinus (arrow) (F). Fewer lymph nodes with metastasis were found in the therapeutic groups. Metastatic tumor cells were observed in subcapsular sinus (G, arrow). Metastatic foci in the lung of the pVec, pesVEGFR-2 and pEndo groups (H-J, scale bar = 200 μm). Many metastatic foci and nodules with small to large were seen in the pVec group (H). Metastatic lung foci were much smaller in the pesVEGFR-2 (I) group than in the control group (J). No metastatic foci were observed in the lung of mouse given pEndo (J). A-C and E-J, H&E stain; D, p53 immunohistochemistry.