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

被引:151
作者
McAlpine, Jessica N. [1 ]
Wiegand, Kimberly C. [2 ]
Vang, Russell [3 ]
Ronnett, Brigitte M. [3 ]
Adamiak, Anna [4 ]
Koebel, Martin [4 ]
Kalloger, Steve E. [2 ]
Swenerton, Kenneth D. [5 ]
Huntsman, David G. [2 ,4 ]
Gilks, C. Blake [2 ,4 ]
Miller, Dianne M. [1 ]
机构
[1] Univ British Columbia, Dept Obstet & Gynaecol, Vancouver, BC V5Z 1M9, Canada
[2] BC Canc Agcy, Ctr Translat & Appl Genom, Vancouver, BC, Canada
[3] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA
[4] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada
[5] BC Canc Agcy, Dept Med Oncol, Vancouver, BC, Canada
关键词
IN-SITU HYBRIDIZATION; HUMAN GASTRIC-CANCER; HUMAN-BREAST-CANCER; GENE AMPLIFICATION; IMMUNOHISTOCHEMICAL EXPRESSION; MONOCLONAL-ANTIBODY; ANTI-HER2; ANTIBODY; TUMORS; CHEMOTHERAPY; GROWTH;
D O I
10.1186/1471-2407-9-433
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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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页数:12
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