HER2 Status in Ovarian Carcinomas: A Multicenter GINECO Study of 320 Patients

Marianne Tuefferd,Sophie Camilleri-Broët,Jean-Paul Guastalla,Martin Combe,Jérôme Couturier,Eric Pujade-Lauraine,Frédérique Penault-Llorca,Anne Vincent-Salomon,Philippe Broët,Djelila Allouache,Béatrice Weber

doi:10.1371/journal.pone.0001138

Abstract

BackgroundDespite a typically good response to first-line combination chemotherapy, the prognosis for patients with advanced ovarian cancer remains poor because of acquired chemoresistance. The use of targeted therapies such as trastuzumab may potentially improve outcomes for patients with ovarian cancer. HER2 overexpression/amplification has been reported in ovarian cancer, but the exact percentage of HER2-positive tumors varies widely in the literature. In this study, HER2 gene status was evaluated in a large, multicentric series of 320 patients with advanced ovarian cancer, including 243 patients enrolled in a multicenter prospective clinical trial of paclitaxel/carboplatin-based chemotherapy.Methodology/Principal FindingsThe HER2 status of primary tumors and metastases was evaluated by both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis of paraffin-embedded tissue on conventional slides. The prognostic impact of HER2 expression was analyzed. HER2 gene was overexpressed and amplified in 6.6% of analyzed tumors. Despite frequent intratumoral heterogeneity, no statistically significant difference was detected between primary tumors and corresponding metastases.Conclusions/SignificanceOur results show that the decision algorithm usually used in breast cancer (IHC as a screening test, with equivocal results confirmed by FISH) is appropriate in ovarian cancer. In contrast to previous series, HER2-positive status did not influence outcome in the present study, possibly due to the fact that patients in our study received paclitaxel/carboplatin-based chemotherapy. This raises the question of whether HER2 status and paclitaxel sensitively are linked.

Highlights

Because symptoms are usually absent, 70 to 80% of patients with ovarian cancer will have advanced disease at the time of diagnosis [1]
HER2-positive status is associated with a poor prognosis [3], and identifies patients who could benefit from anthracycline-based regimens [4]
There are several possible explanations for the wide variation and the relatively low rate of HER2 positivity reported in our series, including the different detection methods used (IHC, fluorescence in situ hybridization (FISH) and chromogenic in situ hybridization), different sources of material, and variations in IHC assay techniques (CB-11, HercepTest or a non-commercial antibody); in addition, variance in staining protocols and subjective interpretation of sample stains makes direct comparison of studies difficult

Summary

Introduction

Because symptoms are usually absent, 70 to 80% of patients with ovarian cancer will have advanced disease at the time of diagnosis [1]. Despite a typically good response to first-line combination chemotherapy, the prognosis for patients with advanced ovarian cancer remains poor because of acquired chemoresistance. HER2 gene status was evaluated in a large, multicentric series of 320 patients with advanced ovarian cancer, including 243 patients enrolled in a multicenter prospective clinical trial of paclitaxel/carboplatin-based chemotherapy. In contrast to previous series, HER2-positive status did not influence outcome in the present study, possibly due to the fact that patients in our study received paclitaxel/carboplatin-based chemotherapy. This raises the question of whether HER2 status and paclitaxel sensitively are linked

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Conclusion