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

Tuefferd, Marianne; Couturier, Jérôme; Penault‐Llorca, Frédérique; Vincent‐Salomon, Anne; Broët, Philippe; Guastalla, Jean‐Paul; Allouache, Djelila; Combe, M.; Weber, B.; Pujade-Lauraine, Éric; Camilleri-Broët, Sophie

doi:10.1371/journal.pone.0001138

Cited by 159 publications

(134 citation statements)

References 42 publications

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“…Inconsistent results have been published with respect to the HER2 expression but the most recent studies seem to agree that only a minority of ovarian cancer overexpress HER2 (9,18,24,25). This was also seen in our study where only a small group of the ovarian cancer patients showed 2+ or 3+ overexpression by immunohistochemistry.…”

Section: Discussionsupporting

confidence: 86%

See 1 more Smart Citation

Protein levels and gene expressions of the epidermal growth factor receptors, HER1, HER2, HER3 and HER4 in benign and malignant ovarian tumors

Steffensen¹,

Waldstrøm²,

Andersen³

et al. 2008

Int J Oncol

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Section: Discussionsupporting

confidence: 86%

“…Despite the numerous studies on the expression and clinical significance of HER1 (4-6) and HER2 (3,(7)(8)(9), the role of these receptors are still controversial in ovarian cancer. Furthermore, only few studies have described the tissue expression of the HER3 and HER4 receptor protein in ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

Protein levels and gene expressions of the epidermal growth factor receptors, HER1, HER2, HER3 and HER4 in benign and malignant ovarian tumors

Steffensen¹,

Waldstrøm²,

Andersen³

et al. 2008

Int J Oncol

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“…Three patients had cerbB2 2+ disease and, considering breast cancer pathology and HER2 positivity criteria, it would have been helpful to perform in situ hybridization techniques to evaluate HER2 gene amplification at least in these patients. Nevertheless, a previous study demonstrated that 100% of cerbb2 3+ cases were HER2 amplified, while only 25% of cerbB2 2+ cases were also FISH + (Tuefferd et al, 2007). Therefore, the lack of FISH analysis in this study is not a deficiency.…”

Section: Discussionmentioning

confidence: 61%

“…The prognostic role of HER2 overexpression in EOC remains unclear. Some studies proposed that an elevated HER2 level was associated with poorer survival (Lassus et al, 2004;Steffensen et al, 2007), whereas other studies could not demonstrate any association (Verri et al, 2005;Tuefferd et al, 2007). In the meta-analysis conducted by Zhao et al (2013), the prognostic effect of HER2 overexpression was also explored; after reviewing eight studies, they demonstrated that HER2 overexpression was significantly associated with poorer overall survival.…”

Section: Discussionmentioning

confidence: 99%

Hormone Receptor, HER2/NEU and EGFR Expression in Ovarian Carcinoma - is here a Prognostic Phenotype?

Demir¹,

Yiğit²,

Sadullahoğlu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Purpose: We aimed to evaluate the effects of hormone receptor, HER2, and epidermal growth factor receptor (EGFR) expression on epithelial ovarian cancer (EOC) prognosis and investigate whether or not phenotypic subtypes might exist. Materials and Methods: The medical records of 82 patients who were diagnosed with EOC between 2003 and 2012 and treated by platinum-based chemotherapy were retrospectively evaluated. Expression of EGFR, oestrogen (ER), progesterone (PR), and cerbB2 (HER2) receptors were assessed immunohistochemically on paraffin-embedded tissues of these patients. Three phenotypic subtypes were defined according to ER, PR, and HER2 expression and associations of these with EGFR expression, clinicopathologic features, platinum sensitivity, and survival were investigated. Results: When we classified EOC patients into three subtypes, 63.4% had hormone receptor positive (HR(+)) (considering breast cancer subtypes, luminal A), 18.3% had triple negative, and 18.3% had HER2(+) disease. EGFR positivity was observed in 37 patients (45.1%) and was significantly more frequent with advanced disease (p=0.013). However, no significant association with other clinicopathologic features and platinum sensitivity was observed. HER2(+) patients had significantly poorer outcomes than HER2(-) counterparts (triple negative and HR positive patients) (p=0.019). Multivariate analysis demonstrated that the strongest risk factor for death was residual disease after primary surgery. Conclusions: Triple negative EOC may not be an aggressive phenotype as in breast cancer. The HER2 positive EOC has more aggressive behaviour compared to triple negative and HR(+) phenotypes. EGFR expression is more frequent in advanced tumours, but is not related with poorer outcome. Additional ovarian cancer molecular subtyping using gene expression analysis may provide more reliable data.

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“…Her-2 is also a target for novel therapeutic approaches, such as trastuzumab, a recombinant antibody designed to block signaling through the Her-2 receptor. Her2 expression in ovca shows rates of 1.8-76%, but data related to its prognostic value are controversial (16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Tumor- and stromal cell-specific expression of topoisomerase IIα and HER-2/neu in primary and recurrent ovarian cancer: Results of a prospective study

Chekerov

Koensgen²,

Rosenthal³

et al. 2009

Mol Med Rep

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Abstract. The aim of the present study was to evaluate the expression of topoisomerase iiα (ToP2a) and Her-2 in tumor epithelial and adjacent stromal cells in ovarian cancer (ovca). immunohistochemistry for ToP2a and Her-2 was performed on 50 ovca specimens from the Tumor Bank of ovarian cancer, and was correlated to established clinicopathological parameters. ToP2a was expressed in 98% and Her-2 in 52% of the ovca specimens. Moderate expression of ToP2a was detected in 72% of the adjacent stromal cells. ToP2a and Her-2 were strongly expressed in the tumor epithelial cells of primary ovca, but reduced in recurrent ovca. Stromal expression of ToP2a increased in recurrent ovca after platinum-based chemotherapy. in conclusion, distinct epithelial and stromal cell expression of ToP2a and Her-2 is a novel feature in the tumor biology of ovca. differential cellular expression of ToP2a in relation to previous chemotherapy probably reflects a modified activity of the 'stromal compartment' in drug resistance. Thus, analysis of ToP2a expression in tumor and stromal ovca cells can aid in identifying subgroups of patients who may have a more favorable response to chemotherapy. Introductionovarian cancer (ovca) has the highest mortality rate of all female gynaecological cancers, with an overall 5-year survival rate of approximately 30% (1,2). at the time of primary diagnosis, most patients have advanced stage disease (Figo iii/iv) (3,4). cytoreductive surgery is known to have a strong prognostic effect on survival (4-6). despite the initial high response rates of current standard chemotherapy with carboplatin and paclitaxel, most patients relapse and soon succumb to the disease due to tumor progression (1). unfortunately, the complex mechanisms of platinum resistance are still poorly understood (7). Thus, the confirmation of novel molecular factors is a promising strategy that may help to individualize chemotherapy for ovca.Topoisomerase iiα (ToP2a) is an important proliferation marker in solid cancer (8,9), with significant expression during the S and g2-M phases (9,10). ToP2a is also the cellular target of anticancer drugs such as etoposide and doxorubicin (11), and has been implicated in contributing to atypical multidrug resistance in ovca (12,13). nonetheless, it does not appear to predict resistance as strongly as other factors. only a few studies have evaluated ToP2a expression in ovca cells, most describing increased amplification in advanced tumor stages associated with poor clinical outcome (8).The Her-2 proto-oncogene is essential for tumor growth and proliferation, with a wide range of amplification in solid tumors (14-16). different ligands can bind through its extracellular segments, and can mediate intracellular signal transduction through tyrosine kinase activity. Her-2 is also a target for novel therapeutic approaches, such as trastuzumab, a recombinant antibody designed to block signaling through the Her-2 receptor. Her2 expression in ovca shows rates of 1.8-76%, but data related to its prognostic value ar...

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

Cited by 159 publications

References 42 publications

Protein levels and gene expressions of the epidermal growth factor receptors, HER1, HER2, HER3 and HER4 in benign and malignant ovarian tumors

Protein levels and gene expressions of the epidermal growth factor receptors, HER1, HER2, HER3 and HER4 in benign and malignant ovarian tumors

Hormone Receptor, HER2/NEU and EGFR Expression in Ovarian Carcinoma - is here a Prognostic Phenotype?

Tumor- and stromal cell-specific expression of topoisomerase IIα and HER-2/neu in primary and recurrent ovarian cancer: Results of a prospective study

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