The role of the HER-2/neu 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 receptor for epidermal growth factor. Aberrant HER-2/neu protein overexpression occurs in human gynecologic adenocarcinomas, including those of the ovary, endometrium, breast, fallopian tube, and cervix, and is secondary to gene amplification and/or overexpression of the p185HER2 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 factor for survival from 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 of patients with 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 E1A delivery to overexpressing tumor cells.


CONCLUSIONS
HER-2/neu appears to play an important role in the biologic behavior of ovarian, endometrial, and breast cancers and holds potential as a target for oncogene-directed therapies.
Cirisano
F D
FD
Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Karlan
B Y
BY
D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000235:genetics / Q000401:mortality; D016889:Endometrial Neoplasms / Q000235:genetics / Q000401:mortality; D005185:Fallopian Tube Neoplasms / Q000235:genetics / Q000401:mortality; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D005833:Genital Neoplasms, Female / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D006801:Humans; D016239:MEDLINE; D010051:Ovarian Neoplasms / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis; D015996:Survival Rate; D014158:Transcription, Genetic; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000401:mortality
D014408:Biomarkers, Tumor; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human