HER2/neu

Low risk Node-negative and all the following pathologic tumor size of 2 cm or less, or grade 1, absence of peritu-moral vascular invasion, HER2/neu gene neither overexpressed nor amplified, and age 35 years or older... 

Node positive (1-3 involved nodes) and HER2/neu gene overexpressed or amplified... 

Cabioglu N, Summy J, Miller C, et al. CXCL-12/stromal cell-derived factor-la transactivates HER2-neu in breast cancer cells by a novel pathway involving src kinase activation. Cancer Res 2005 65 6493-6497. 

Figure 5.2 Comparison of immunohistochemical staining results among variable periods, 6 h to 30 days, of formalin-fixed, paraffin-embedded human breast cancer tissue (A-N), and cell line MCF-7 sections (O-Bl). All four markers, estrogen receptor (ER) (A-G), CK (cytokeratin cocktail, H-N), Her2/neu (O-U), and MIB-1 (V-Bl), showed comparable positive immunostaining results at +++ level after antigen retrieval. Original magnification x 200. Bar = 50 tm. Reproduced with permission from Shi et al., I Histochem. Cytochem. 2007 55 105-109. See color insert.

As mentioned above, our studies and other articles demonstrate substantially complete restoration of immunoreactivity (AR rate = 100%) for many antigens (proteins) exemplified by ER, progesterone receptor (PR), HER2/neu,... 

These principles are supported by a related set of studies that showed reliable inter-laboratory IHC staining for Her2/neu, ER, and so on could be achieved based on optimal AR-IHC protocols and stringent quality control using standard reference materials, even though ischemia time itself was uncontrolled and unknown.38 0... 

Fig. 24 HER2/neu antibody-conjugated poly(amino acid)-coated iron oxide nanoparticles for breast cancer cell imaging. The part labeled as 1 is shown enlarged. (Adapted from [79])...

Treatment of Her2/neu (EGFR2)-upregulated breast cancers with Herceptin... 

Baselge, ]., et al., "Recombinant Humanized Anti-HER2 Antibody (HERCEPTIN) Enhances the Antitumor Activity of Paclitaxel and Doxorubicin Against HER2/neu Overexpressing Human Breast Cancer Xenografts," Cancer Res., 58, 2825-2831 (1998). 

Herceptin attaches to the HER2/neu receptor and activates the complement system (a series of serum and cell-associated proteins involved in immune response) to destroy those cells expressing such receptors. Through this action, Herceptin disrupts the signaling pathway for breast cancer cell proliferation (refer to diagram below). 

Nagata Y, et al. Peptides derived from a wild-type murine proto-oncogene c-erbB-2/HER2/neu can induce CTL and tumor suppression in syngeneic hosts. J Immunol 1997 159 1336. 

Baselga, J., D. Tripathy, J. Mendelsohn, S. Baughman, C. C. Benz, L. Dantis, N. T. Sklarin, A. D. Seidman, C. A. Hudis, J. Moore, P. P. Rosen, T. Twaddell, I. C. Henderson, and L. Norton. Phase II study of weekly intravenous trastuzumab (Herceptin) in patients with HER2/neu-overexpressing metastatic breast cancer. Semin Oncol. 26 78-83.1999. 

ErbB2/HER2/Neu Overexpression, point mutations Breast, ovarian, gastric, NSCL, colon... 

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