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HER-2 (p185 ERBB2, C-erb B2, NEU-protooncogene)

The human HER-2 (p158 HER-2, c-erbB-2, neu) gene encodes a putative transmembrane growth factor receptor (p185 protein) that is closely related to the epidermal growth factor receptor protein. The HER-2 gene product is a 185 kDa glycoprotein that contains an extracellular ligand-binding domain and intracellular tyrosine kinase activity. HER-2 protein staining is observed only in low levels in epithelial cells of most organs in normal human tissues and at slightly higher levels in fetal tissues. Both HER-2 oncogene amplification and oncoprotein overexpression have been analyzed for potential utility in diagnostic and prognostic tests for: breast, ovarian, gastric, lung; and other cancers. In these malignancies the HER-2 oncoprotein overexpression is correlated with a poor prognosis. In 15–40 % of primary breast cancers, amplification of the HER-2 oncogen is found which is highly correlated with overexpression of the encoded 185 kDa protein and seems to play a major role especially during the initiation of ductal carcinomas. HER-2 protein overexpression is described as independent prognostic factor with greater predictive power than most of the currently used prognostic tools – especially in axillary lymph-node-positive breast cancer patients. Studies analyzing small series of patients have suggested a prognostic value for HER-2 oncoprotein expression in axillary node negative (ANN) patients. An association between oncoprotein expression and decreased overall survival among ANN patients with good nuclear grade tumors has been demonstrated. In addition it has been reported that in low risk patients (estrogen receptor positive, small tumors), HER-2 protein expression was associated with early recurrence. Data demonstrate the large body of evidence implicating HER-2 oncoprotein in the biology and prognosis of breast carcinoma.

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