Significance of epidermal growth factor receptor in advanced ovarian cancer.

Scambia, Giovanni; Panici, P. Benedetti; Battaglia, Federica; Baiocchi, G.; Greggi, Stefano; Vincenzo, Rosa De; Mancuso, Stefano

doi:10.1200/jco.1992.10.4.529

Cited by 87 publications

(45 citation statements)

References 29 publications

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“…Whereas the frequency of ErbB2 overexpression is low, the frequencies of ErbB3 and ErbB4 expressions are high in OVCA. Univariate and multivariate statistical analyses have confirmed that EGFR overexpression is significantly associated with a high risk of progression in OVCA patients (Scambia et al, 1992). Seven ligands have been described for EGFR: EGF, transforming growth factor-a (TGF-a).…”

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confidence: 97%

Clinical significance of heparin-binding epidermal growth factor-like growth factor in peritoneal fluid of ovarian cancer

et al. 2005

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Epidermal growth factor receptor (EGFR) has been implicated in tumour growth and extension of ovarian cancer. Peritoneal fluid in ovarian cancer patients contains various growth factors that can promote tumour growth and extension. In order to investigate the clinical significance of EGFR ligands as activating factors of ovarian cancer, we examined the cell proliferation-promoting activity and the level of EGFR ligands in peritoneal fluid obtained from 99 patients. Proliferation-promoting activity in peritoneal fluid from 63 ovarian cancer patients (OVCA) was much higher than peritoneal fluid from 18 ovarian cyst patients (OVC) and 18 normal ovary patients (NO), and the activity was suppressed only by antibodies against EGFR or heparin-binding epidermal growth factor (HB-EGF). A large difference was observed in the level of EGFR ligands between HB-EGF and TGF-a or amphiregulin. The concentration of HB-EGF in OVCA significantly increased compared to that in OVC or NO (Po0.01). No significant difference in the concentration of TGF-a and amphiregulin was found between the OVCA and NO or OVC groups. In peritoneal fluid, HB-EGF is sufficiently elevated to activate cancer cells even at an early stage of OVCA. These results suggested that HB-EGF in peritoneal fluid might play a key role in cell survival and in the proliferation of OVCA.

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confidence: 97%

Clinical significance of heparin-binding epidermal growth factor-like growth factor in peritoneal fluid of ovarian cancer

et al. 2005

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“…Ovarian tumors are pathologically heterogeneous, and although the initiating events in ovarian tumor development are poorly understood, ovarian tumorigenesis is characterized by multiple genetic alterations and molecular signatures (2). The epidermal growth factor (EGF) receptor (EGFR) is overexpressed or mutated in a wide variety of human tumors including ovarian carcinomas (3)(4)(5)(6)(7)(8). Cellular responses to EGFR activation include those that play a critical role in tumor growth, survival, and progression, whereas EGFR overexpression in tumors has been associated clinically with progression and metastasis (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

PEA3 Is Necessary for Optimal Epidermal Growth Factor Receptor–Stimulated Matrix Metalloproteinase Expression and Invasion of Ovarian Tumor Cells

Dahl

Zeineldin

Hudson

2007

Molecular Cancer Research

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Elevated expression of the epidermal growth factor (EGF) receptor (EGFR) is detected in human ovarian tumors and is associated with decreased recurrence-free and overall survival. EGFR activation affects tumor progression in part by promoting tumor invasion through the induction of prometastatic matrix metalloproteinases (MMP). PEA3, an ETS family transcription factor, is elevated in advanced and metastatic ovarian cancer and regulates MMPs in various cell types, therefore, we investigated whether PEA3 is required for the EGFR-dependent induction of MMP mRNA. MMP-9 and MMP-14 mRNA levels were selectively increased in response to EGFR activity in ovarian tumor cells. EGFR activation resulted in nuclear accumulation of PEA3 and direct binding of PEA3, but not the related protein ETS-1, to the endogenous MMP-9 and MMP-14 promoters. Furthermore, PEA3 overexpression was sufficient to induce MMP-9 and MMP-14 mRNA, tumor cell migration, and invasion, suggesting that PEA3 is an important contributor to the metastatic phenotype. Additionally, inhibition of PEA3 expression via short interfering RNA reduced the EGF induction of MMP-9 and MMP-14 gene expression by 92% and 50%, respectively, and impaired EGF-stimulated tumor cell invasion. These results suggest that PEA3 is regulated by EGFR and that the elevated PEA3 expression detected in human ovarian cancer may divert cells to a more invasive phenotype by regulating MMP-9 and MMP-14. (Mol Cancer Res 2007;5(5):413 -21)

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“…Both c-erbB-1 (EGFR) and c-erbB-2 overexpression have been associated with aggressive behaviour in a series of solid tumours, including breast (Sainsbury et al, 1987;Slamon et al, 1989), cervix (Gullick et al, 1988Pfeiffer et al, 1989) and ovary (Bauknecht et al, 1988;Berchuck et al, 1990;Scambia et al, 1992). In contrast, considerably less is known about the involvement of c-erbB-3 in malignancy.…”

Section: Discussionmentioning

confidence: 99%

“…Gene amplification and protein overexpression of receptor tyrosine kinases including the epidermal growth factor receptor (EGFR) and c-erbB-2 protein have been associated with the induction and progression of a number of human cancers (Sainsbury et al, 1987;Bauknecht et al, 1988;Gullick et al, 1988;Slamon et al, 1989;Berchuck et al, 1990Berchuck et al, , 1991Scambia et al, 1992). A relatively new member of this type I growth factor receptor family, c-erbB-3, has also been characterised (Kraus et al, 1989;Plowman et al, 1990), although clarification of its biological role awaits identification of a specific ligand.…”

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c-erbB-3 protein expression in ovarian tumours

Simpson

Weatherill²,

Miller³

et al. 1995

Br J Cancer

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Summary In this study the expression of c-erbB-3 protein was investigated in a range of human ovarian tumours using a monoclonal antibody (RTJ1) raised to a synthetic peptide from the cytoplasmic domain of the human c-erbB-3 protein. A total of 73 samples from 71 patients were graded as negative, weak, moderate or strong according to the intensity of immunohistochemical staining observed, and this was related to tumour characteristics and other clinical parameters. In terms of positivity vs negativity, of the 73 samples examined, 62 (85%) showed positive immunohistochemical staining for c-erbB-3. The majority of all ovarian tumours studied were positive for c-erbB-3 regardless of whether they were malignant (89%), borderline (100%) or benign (61%), however the incidence of positivity was significantly less in the benign group than in overtly malignant tumours (P = 0.03). c-erbB-3 positivity was not significantly associated with either age at diagnosis, tumour stage, differentiation, ploidy, percentage in S-phase or post-operative tumour bulk in malignant tumours. In terms of intensity of staining no significant difference was observed either within the common epithelial group or between this group and tumours of a benign nature. A significantly more intense pattern of c-erbB-3 staining was observed in tumours of borderline malignancy when compared with their overtly malignant counterparts (P = 0.002). Patients presenting with early-stage malignant tumours (I/II) were more likely to display intense tumour staining than those with late-stage disease (III/IV) (P = 0.04). These investigations suggest that c-erbB-3 protein is frequently expressed in both benign and malignant ovarian tumours, and that overexpression is more common in borderline and early invasive lesions. Keywords: c-erb-3; ovarian tumoursAbnormal expression of a number of growth factors and their receptors has been linked with prognosis and disease outcome in many diverse tumour types, including ovarian cancer (Berns et al., 1992;Kohler et al., 1992;Bauknecht et al., 1993). Gene amplification and protein overexpression of receptor tyrosine kinases including the epidermal growth factor receptor (EGFR) and c-erbB-2 protein have been associated with the induction and progression of a number of human cancers (Sainsbury et al., 1987;Bauknecht et al., 1988;Gullick et al., 1988;Slamon et al., 1989; Berchuck et al., 1990Berchuck et al., , 1991Scambia et al., 1992). A relatively new member of this type I growth factor receptor family, c-erbB-3, has also been characterised (Kraus et al., 1989;Plowman et al., 1990), although clarification of its biological role awaits identification of a specific ligand.c-erbB-3 protein has been found in normal human adult and fetal tissues, including the ovary (Prigent et al., 1992), and has also been shown to be expressed at both the mRNA and protein levels in a number of tumour cell lines and primary tumour material (Lemoine et al., 1992;Rajkumar et al., 1993). Rajkumar et al. (1993) have described the production of a monoc...

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Significance of epidermal growth factor receptor in advanced ovarian cancer.

Abstract: Data reported here suggest that the presence of EGF-R in advanced ovarian tumor at the time of the primary surgery identifies a subset of patients with a particularly poor prognosis.

Cited by 87 publications

References 29 publications

Clinical significance of heparin-binding epidermal growth factor-like growth factor in peritoneal fluid of ovarian cancer

Clinical significance of heparin-binding epidermal growth factor-like growth factor in peritoneal fluid of ovarian cancer

PEA3 Is Necessary for Optimal Epidermal Growth Factor Receptor–Stimulated Matrix Metalloproteinase Expression and Invasion of Ovarian Tumor Cells

c-erbB-3 protein expression in ovarian tumours

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