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Multicenter Study
. 2009 Jun;113(3):341-7.
doi: 10.1016/j.ygyno.2009.02.009. Epub 2009 Mar 9.

Associations between ERBB2 amplification and progression-free survival and overall survival in advanced stage, suboptimally-resected epithelial ovarian cancers: a Gynecologic Oncology Group Study

John Farley  1 , Sartoru Fuchiuji, Kathleen M Darcy, Chunqiao Tian, William J Hoskins, William P McGuire, Parviz Hanjani, David Warshal, Benjamin E Greer, Jerome Belinson, Michael J Birrer
Affiliations
Multicenter Study

Associations between ERBB2 amplification and progression-free survival and overall survival in advanced stage, suboptimally-resected epithelial ovarian cancers: a Gynecologic Oncology Group Study

John Farley et al. Gynecol Oncol. 2009 Jun.

Abstract

Objective(s): The Gynecologic Oncology Group (GOG) examined the association between ERBB2 amplification and clinical covariates, tumor response, disease status post-chemotherapy, progression-free survival (PFS), and overall survival (OS) in epithelial ovarian cancer (EOC).

Methods: Women with suboptimally-resected, advanced stage EOC who participated in GOG-111, a multi-center randomized phase III trial of cyclophosphamide+cisplatin versus paclitaxel+cisplatin, and provided a tumor block through the companion protocol GOG-9404 were eligible. ERBB2 amplification was examined using fluorescence in situ hybridization (FISH) with probes for ERBB2 and the centromere of chromosome 17 (CEP17).

Results: ERBB2 amplification, defined as >2 copies of ERBB2/CEP17, was a rare event in EOC with 7% (9/133) of women exhibiting between 2.2 and 33.7 copies of ERBB2/CEP17, and was not associated with patient age, race, GOG performance status, stage, cell type, grade, measurable disease status, volume of ascites, tumor response or disease status post-chemotherapy. Women with >2 verses < or =2 copies of ERBB2/CEP17 did not have a reduced risk of disease progression (hazard ratio [HR]=0.56; 95% confidence interval [CI]=0.27-1.16; p=0.120) or death (HR=0.57; 95% CI=0.26-1.23; p=0.152), and ERBB2 amplification was not an independent prognostic factor for PFS or OS. ERBB2 amplification, defined as >4 copies of ERBB2/nuclei, was observed in 9% (12/133) of women with levels ranging from 4.2 to 49.2 copies of ERBB2/nuclei, and was associated with older age and volume of ascites, but not with the other clinical covariates or outcome.

Conclusion(s): ERBB2 amplification is a rare event and has no predictive or prognostic value in suboptimally-resected, advanced stage EOC treated with platinum-based combination chemotherapy.

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Conflict of interest statement

Conflict of interest statement

The authors declare that there are no conflicts of interest with the exception of Dr. William J. Hoskins who reports that he is CoChair NCI Gynecologic Cancer Steering Committee, Member of the Executive Board of ACOG, Investor of Chestnut Medical and his spouse is the Vice President of the ACOG.

Figures

Fig. 1.
Fig. 1.
FISH analysis. Representative FISH analysis of ERBB2 labeled with SpectrumOrange and CEP17 labeled with SpectrumGreen illustrating a normal ratio (A), and amplification of ERBB2 (B).
Fig. 2.
Fig. 2.
Kaplan–Meier estimate of progression-free survival (A) and overall survival (B) for women with or without ERBB2 amplification defined as >2 copies of ERBB2/CEP17. Censored indicates patients who were alive with no evidence of disease progression. Logrank test was used to evaluate the equality in progression-free survival (p = 0.115) and survival (p = 0.147) distributions between women with or without ERBB2 amplification defined as >2 copies of ERBB2/CEP17.
Fig. 3.
Fig. 3.
Kaplan–Meier estimate of progression-free survival (A) and overall survival (B) for women with normal, borderline or amplified ERBB2/nuclei copies. Censored indicates patients who were alive with no evidence of disease progression. Logrank test was used to evaluate the equality in progression-free survival (p = 0.730) and survival (p = 0.980) distributions between women with normal and amplified ERBB2/nuclei copies.
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