Pathogenesis of ovarian cancers.
OBJECTIVE
To review our current understanding of the molecular genetic events involved in the development of epithelial ovarian cancers.


METHODS
Molecular biologic techniques have been used to examine the role of growth-stimulatory genes (oncogenes) and -inhibitory genes (tumor suppressors) in ovarian cancer.


RESULTS
A number of different peptide growth factors and their receptors are expressed by normal and malignant ovarian epithelial cells. However, the role, if any, of growth factors in ovarian carcinogenesis or maintenance of the transformed phenotype remains unknown. Amplification and overexpression of the HER-2/neu and c-myc oncogenes occur in a significant fraction of epithelial ovarian cancers (20-30%). Overexpression of HER-2/neu has correlated with poor survival in some studies, whereas c-myc amplification is more common in serous cancers. Mutation of the K-ras oncogene frequently occurs in borderline ovarian tumors, but is less common in invasive epithelial ovarian cancers. Mutation of the p53 tumor suppressor gene occurs in approximately half of advanced (stage III/IV) ovarian cancers and in 15% of early (stage IA/IB) cases. Most recently, preliminary studies have focused on the role of other tumor suppressor genes, cyclins, WAF1, and DNA mismatch repair genes.


CONCLUSIONS
An understanding of the molecular events involved in the pathogenesis of epithelial ovarian cancer is beginning to evolve. Improvements in early diagnosis, treatment, and prevention of this deadly disease are dependent on further progress in this area.
Berchuck
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A
Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710, USA.
Elbendary
A
A
Havrilesky
L
L
Rodriguez
G C
GC
Bast
R C
RC
D002277:Carcinoma / Q000235:genetics*; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D016147:Genes, Tumor Suppressor; D006131:Growth Inhibitors / Q000502:physiology; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D009857:Oncogenes; D010051:Ovarian Neoplasms / Q000235:genetics*; D017978:Receptors, Growth Factor / Q000502:physiology
D006131:Growth Inhibitors; D006133:Growth Substances; D017978:Receptors, Growth Factor; D019204:GTP-Binding Proteins