HER2 overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy
- PMID: 20003286
- PMCID: PMC2803495
- 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
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.
Figures
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References
-
- Winter W E III, Maxwell GL, Tian C, Carlson J W, Ozols R F, Rose P G, Markman M, Armstrong Deborah K, Muggia Franco, McGuire William P. Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007;25:3621–7. doi: 10.1200/JCO.2006.10.2517. - DOI - PubMed
-
- Pectasides D, Fonutrilas G, Aravantinos G, Kalofonos Haralampos P, Efstathiou E, Salamalekis E, Farmakis D, Skarlos D, Briasoulis E, Economopoulos T, Dimopoulos MA. Advanced stage mucinous epithelial ovarian cancer; the Hellenic Cooperative Oncology Group experience. Gynecol Oncol. 2005;99:7988–90. doi: 10.1016/j.ygyno.2005.07.022. - DOI - PubMed
-
- Tabrizi AD, Kalloger SE, Köbel M, Cipollone J, Roskelley CD, Mehl E, Gilks CB. Primary ovarian mucinous carcinoma of intestinal type. Analysis of histologic invasion patterns, survival and immunohistochemical expression profile in a series of 31 cases. Int J Gynecol Path. 2009. in press . - PubMed
-
- Pignata S, Ferrandina G, Scarfone G, Scollo P, Odicino F, Cormio G, Katsaros D, Villa A, Mereu L, Ghezzi F, Manzione L, Lauria R, Breda E, Alletti DG, Ballardini M, Lombardi A V, Sorio R, Mangili G, Priolo D, Magni G, Morabito A. Activity of chemotherapy in mucinous ovarian cancer with a recurrence free interval of more than 6 months: resuls from the SOCRATES restrospective study. BMC Cancer. 2008;8:252. doi: 10.1186/1471-2407-8-252. - DOI - PMC - PubMed
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