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.

Cancer Research
|April 6, 2001
PubMed

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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