C-erbB2 oncoprotein and its soluble ectodomain: a new potential tumor marker for prognosis early detection and monitoring patients undergoing Herceptin treatment

c-erbB-2 oncoprotein (or p185) coded by c-erbB-2 oncogene can be extracted with detergent from cell membrane of breast tissue and breast tumor cell line. The ectodomain of p185 can be cleaved proteolytically from the transmembrane receptor and released into solution. In blood circulation, only the ectodomain can be found, whereas only p185 exists in the extracts of tissue and cell line. p185 can also be quantified in the fine-needle aspirate biopsies and the concentration of p185 from the biopsies of malignant breast tissue is much higher than that of the normal and benign tissue. Measuring the ectodomain of the c-erbB-2 oncoprotein not only is useful to identify breast cancer patient who will benefit from Herceptin treatment but also can be used to monitor patients during the treatment. Overexpression of p185 and the elevation of circulating ectodomain is usually associated with poor prognosis. Overexpression of p185 in breast cancer patients with positive estrogen receptor identifies a subgroup of patients who will not respond to the endocrine therapy. Activation of p185 appears to be an early event in tumorigenesis for some cancers. It is possible that the ectodomain could be used as an early tumor marker detecting benign disease.