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. 2009 Dec 10:9:433.
doi: 10.1186/1471-2407-9-433.

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

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

Jessica N McAlpine et al. BMC Cancer. .

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.

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Figures

Figure 1
Figure 1
Flowchart outlining the process of case identification for our retrospective series of mucinous ovarian cancers and mucinous borderline ovarian tumors.
Figure 2
Figure 2
Kaplan-Meier survival curves demonstrating that the presence of HER2 amplification in primary mucinous carcinomas is not of prognostic significance with respect to disease recurrence.
Figure 3
Figure 3
HER2 immunostaining and FISH of tumors from cases 1 and 2 (Case 2-sample from lung), who subsequently received trastuzumab either alone or in combination with conventional chemotherapy. Each tumor shows strong immunoreactivity for HER2 and amplification by FISH (HER2 probe -- red, CEP17 probe -- green).
Figure 4
Figure 4
Computed tomography images of Case 1. The first image (a.) was taken four months after completion of (surgery and) chemotherapy treatment for her first recurrence. Imaging had been ordered for increased gastrointestinal symptoms and an elevation in her tumor markers. Ascites and omental disease are noted. Carboplatin and trastuzumab were commenced with a dramatic response (b. resolution of ascites and omental nodules) seen after only three cycles. Graphic representation of CA125 levels (c.) also demonstrates a drop in CA125 levels after the initiation of carboplatin and trastuzamab therapy and stable CA125 levels during trastuzamab monotherapy for at least three cycles.
Figure 5
Figure 5
Prospectively identified Case 3: Tumor from initial presentation classified as a mucinous borderline ovarian tumor (BOT) and shows a discrete area of HER2 positivity in what is predominantly a HER2 negative tumor.

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