The Role of the HER-2lneu Oncogene in Gynecologic Cancers

OBJECTIVE: The HER-2/neu proto-oncogene (also known as c-erbB2, neu, and HER2) encodes a 185-kDa transmembrane glycoprotein with intrinsic tyrosine kinase activity that resembles the receptorfor epidermal growth factor. Aberrant HER-2/neu protein overexpression occurs in human gynecologic adeno-carcinomas, including those of the ovary, endometrium, breast, fallopian tube, and cervix, and is secondary HE2to gene amplification and/or overexpression of the p 185HER protein. METHODS: A Medline literature search revealed numerous studies on HER-2/neu and tumor biology, cancer prognosis, and therapeutic targeting. We present a review of the literature pertinent to gynecologic malignancies. RESULTS: Overexpression of HER-2/neu was found to be a poor prognostic factorfor survivalfrom advanced-stage ovarian cancer, node-positive breast cancer, and endometrial cancer. Although a specific ligand has not been definitively identified, HER-2/neu may have unusually complex activation pathways because it can form both homodimeric and heterodimeric associations with other related receptor proteins. Preliminary findings suggest that serum HER-2/neu levels may be used as a tumor marker in a subset ofpatients uith tumors that overexpress the HER-2/neu receptor. Receptor-targeted therapeutics currently being studied include the use of receptor antibodies, liposomally delivered antisense DNA, antigen-activated cytotoxic lymphocytes, and adenovirus-mediated ElA delivery to overexpressing tumor cells. CONCLUSION: HER-2/neu appears to play an important role in the biologic behavior of ovarian, endometrial, and breast cancers and holds potential as a targetfor oncogene-directed therapies. (J Soc Gyneco