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Pathogenesis of ovarian cancers
A Berchuck1, A Elbendary, L Havrilesky
1Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710, USA.
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.
Insights
Molecular genetic events in epithelial ovarian cancer are being uncovered. Understanding oncogenes and tumor suppressor genes is key for early diagnosis and improved treatment of this deadly disease.
Area of Science:
- Oncology
- Molecular Genetics
- Cancer Biology
Background:
- Epithelial ovarian cancer (EOC) pathogenesis involves complex molecular genetic alterations.
- Identifying these genetic events is crucial for advancing diagnostic and therapeutic strategies.
Purpose of the Study:
- To review the current understanding of molecular genetic events in epithelial ovarian cancer development.
- To highlight the roles of oncogenes and tumor suppressor genes in EOC.
Main Methods:
- Utilized molecular biologic techniques to investigate gene expression and mutations.
- Examined the involvement of growth-stimulatory genes (oncogenes) and inhibitory genes (tumor suppressors).
Main Results:
- Amplification and overexpression of HER-2/neu and c-myc oncogenes occur in 20-30% of EOC.
- p53 tumor suppressor gene mutations are found in approximately half of advanced EOC cases.
- K-ras oncogene mutations are common in borderline tumors but less so in invasive EOC.
Conclusions:
- Understanding the molecular pathogenesis of EOC is evolving.
- Further research into genetic alterations is essential for improving early diagnosis, treatment, and prevention of EOC.