ERBB2 and breast cancer: Although osteosarcoma cell lines and tissue sections were HER2-positive by immunohistochemistry or flow cytometry [11,62], HER2 gene amplification was rarely observed in osteosarcoma, and the expression levels were much lower than those of HER2(+) breast cancers [68], accounting for the clinical insensitivity of OS to trastuzumab [8].