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

McAlpine JN, Wiegand KC, Vang R, Ronnett BM, Adamiak A, Köbel M, Kalloger SE, Swenerton KD, Huntsman DG, Gilks CB, Miller DM - BMC Cancer (2009)

Bottom Line: HER2 amplification in primary mucinous carcinomas was not associated with an increased likelihood of recurrence.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Gynaecology and Obstetrics, University of British Columbia, Vancouver, BC, Canada. jessica.mcalpine@vch.ca

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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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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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.

Mentions: In the third case, evaluation of her response to trastuzumab alone and in combination with platin-based chemotherapy was not possible by RECIST criteria (not imaged pre/post therapy and inconsistent tumor marker assessment). Interestingly, evaluation of her primary presentation, first recurrence and second recurrence showed an apparent change in HER2 amplification status. Careful re-analysis of the primary tumor identified an area of tumor heterogeneity. The primary tumor was predominantly HER2 negative with only focal HER2 expression (Figure 5). The areas showing overexpression also showed HER2 amplification (data not shown). In the recurrent specimens (28 and 57 months from initial diagnosis) there was diffuse HER2 overexpression and amplification.


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

McAlpine JN, Wiegand KC, Vang R, Ronnett BM, Adamiak A, Köbel M, Kalloger SE, Swenerton KD, Huntsman DG, Gilks CB, Miller DM - BMC Cancer (2009)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2803495&req=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.
Mentions: In the third case, evaluation of her response to trastuzumab alone and in combination with platin-based chemotherapy was not possible by RECIST criteria (not imaged pre/post therapy and inconsistent tumor marker assessment). Interestingly, evaluation of her primary presentation, first recurrence and second recurrence showed an apparent change in HER2 amplification status. Careful re-analysis of the primary tumor identified an area of tumor heterogeneity. The primary tumor was predominantly HER2 negative with only focal HER2 expression (Figure 5). The areas showing overexpression also showed HER2 amplification (data not shown). In the recurrent specimens (28 and 57 months from initial diagnosis) there was diffuse HER2 overexpression and amplification.

Bottom Line: HER2 amplification in primary mucinous carcinomas was not associated with an increased likelihood of recurrence.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Gynaecology and Obstetrics, University of British Columbia, Vancouver, BC, Canada. jessica.mcalpine@vch.ca

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.

Show MeSH
Related in: MedlinePlus