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Open Access Highly Accessed Research article

HER2 overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy

Jessica N McAlpine1*, Kimberly C Wiegand2, Russell Vang3, Brigitte M Ronnett3, Anna Adamiak4, Martin Köbel4, Steve E Kalloger2, Kenneth D Swenerton5, David G Huntsman24, C Blake Gilks24 and Dianne M Miller1

Author Affiliations

1 Department of Gynaecology and Obstetrics, University of British Columbia, Vancouver, BC, Canada

2 Center for Translational and Applied Genomics, BC Cancer Agency, British Columbia, Canada

3 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

4 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada

5 Department of Medical Oncology, BC Cancer Agency, Vancouver, BC, Canada

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BMC Cancer 2009, 9:433  doi:10.1186/1471-2407-9-433

Published: 10 December 2009

Abstract

Background

The response rate of ovarian mucinous carcinomas to paclitaxel/carboplatin is low, prompting interest in targeted molecular therapies. We investigated HER2 expression and amplification, and the potential for trastuzumab therapy in this histologic subtype of ovarian cancer.

Methods

HER2 status was tested in 33 mucinous carcinomas and 16 mucinous borderline ovarian tumors (BOT)). Five cases with documented recurrence and with tissue from the recurrence available for testing were analyzed to determine whether HER2 amplification status changed over time. Three prospectively identified recurrent mucinous ovarian carcinomas were assessed for HER2 amplification and patients received trastuzumab therapy with conventional chemotherapy.

Results

Amplification of HER2 was observed in 6/33 (18.2%) mucinous carcinomas and 3/16 (18.8%) BOT. HER2 amplification in primary mucinous carcinomas was not associated with an increased likelihood of recurrence. The prospectively identified recurrent mucinous carcinomas showed overexpression and amplification of HER2; one patient's tumor responded dramatically to trastuzumab in combination with conventional chemotherapy, while another patient experienced an isolated central nervous system recurrence after trastuzumab therapy.

Conclusion

HER2 amplification is relatively common in ovarian mucinous carcinomas (6/33, 18.2%), although not of prognostic significance. Trastuzumab therapy is a treatment option for patients with mucinous carcinoma when the tumor has HER2 amplification and overexpression.