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Published on: May 20, 2014
Overexpression of HER-2 in ovarian carcinomas
I Hellström1, G Goodman, J Pullman
1Program in Tumor Immunology, Pacfic Northwest Research Institute, Seattle, Washington 98122, USA.
Abstract:
The transmembrane receptor encoded by the HER-2 cellular oncogene is amplified in several types of human carcinomas and provides an attractive therapeutic target. Shown by immunohistology, <25% of newly diagnosed ovarian carcinomas express the HER-2 protein. However, now we report that this protein was expressed in all 20 tumor cell lines derived from stage III and IV ovarian cancers as well as in tumor cells harvested from patients with malignant ascites and in tumor samples taken at a second surgery, suggesting that cells with excess expression may have a selective growth advantage. HER-2-positive ovarian carcinoma cells were shown to be sensitive to antibody-dependent cellular cytotoxicity, and their in vitro proliferation was inhibited by anti-HER-2 MAb Herceptin. We postulate, therefore, that therapy which targets HER-2 may be more efficacious in patients with ovarian carcinoma than indicated by the commonly low expression of HER-2 in tumors removed at the time of primary surgery.
Insights
HER-2 protein expression is higher in advanced ovarian cancers, suggesting targeted therapy may be more effective. HER-2-positive cells show sensitivity to Herceptin and antibody-dependent cellular cytotoxicity.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- The HER-2 oncogene encodes a transmembrane receptor amplified in various human carcinomas, making it a therapeutic target.
- HER-2 protein expression is typically low (<25%) in newly diagnosed ovarian carcinomas via immunohistology.
Purpose of the Study:
- To investigate HER-2 protein expression in advanced ovarian cancers (Stage III/IV) and assess its therapeutic implications.
- To evaluate the sensitivity of HER-2-positive ovarian cancer cells to antibody-dependent cellular cytotoxicity and anti-HER-2 monoclonal antibody (MAb) Herceptin.
Main Methods:
- Immunohistology was used to assess HER-2 protein expression.
- Analysis included 20 ovarian tumor cell lines (Stage III/IV), malignant ascites, and tumors from second surgeries.
- In vitro assays evaluated sensitivity to antibody-dependent cellular cytotoxicity and Herceptin treatment.
Main Results:
- HER-2 protein was expressed in all 20 Stage III/IV ovarian tumor cell lines.
- Expression was also detected in tumor cells from malignant ascites and at second surgical interventions.
- HER-2-positive ovarian carcinoma cells demonstrated sensitivity to antibody-dependent cellular cytotoxicity and Herceptin-mediated proliferation inhibition.
Conclusions:
- Elevated HER-2 expression in advanced ovarian cancers suggests a selective growth advantage for these cells.
- Targeted HER-2 therapy, such as with Herceptin, may be more efficacious in ovarian carcinoma patients than initially suggested by low primary tumor expression.
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