Significance of epidermal growth factor receptor expression in primary human endometrial cancer

Scambia, Giovanni; P, Benedetti Panici; Ferrandina, Gabriella; Battaglia, Federica; Distefano, Mariagrazia; D’Andrea, Gabriele; Vincenzo, Rosa De; Maneschi, Francesco; Ranelletti, F O; Mancuso, Stefano

doi:10.1002/ijc.2910560106

Cited by 52 publications

(23 citation statements)

References 21 publications

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“…Furthermore, cell invasiveness was directly proportional to the level of EGFR expression. Similar results were obtained for patients with laryngeal squamous cell carcinoma [20], primary endometrial carcinoma [21], and laryngeal cancer [22]. In the case of primary endometrial carcinoma, Scambia et al [21] revealed that well-differentiated tumors expressed fewer receptors than moderately or poorly differentiated tumors.…”

Section: Role Of Changes In Receptor Expression Density In Health Andsupporting

confidence: 68%

Expression Density of Receptors as a Potent Regulator of Cell Function and Property in Health and Pathology

Sennikov

Alshevskaya

Zhukova

et al. 2018

Int Arch Allergy Immunol

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The expression of cytokine receptors has a crucial role in many cellular processes. Recent studies reported that changes of receptor expression could control the action of mediators on target cells. The initiation of different signaling pathways and, therefore, specific effects on cells, depends on certain components forming the cytokine-receptor complex. These mechanisms control the immune response and affect both the course of diseases (oncological, autoimmune, inflammatory) and the effectiveness of therapy. This review describes the potential of immune mediator receptors to regulate the efficiency of cytokine activity during pathologic processes and ensure the variability of their biological effects. Our aim was to investigate the spectrum of potential roles of changes in mediator receptor expression for main classes of pathologies. For all major types of immune mediators (cytokines, interleukins, chemokines, growth factors, and tumor necrosis factors), it has been shown that changes in their receptor expression are associated with impaired functioning of the organism in chronic diseases.

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Section: Role Of Changes In Receptor Expression Density In Health Andsupporting

confidence: 68%

Expression Density of Receptors as a Potent Regulator of Cell Function and Property in Health and Pathology

Sennikov

Alshevskaya

Zhukova

et al. 2018

Int Arch Allergy Immunol

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“…Most notably, deregulated EGFR activity has been linked to the development, progression and metastatic spread of HNSCC, NSCLC, CRC, breast, ovarian, cervical, bladder, pancreatic, gastric, endometrial and brain cancer. 3,[55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71] In many of these cancers, EGFR expression is associated with decreased overall survival rates. 72 Modes of deregulated EGFR activity have included increased stimulation of the EGFR through ligand binding, 73 point mutations within the receptor, 74 deletion mutants of exons 2-7 of the EGFR (EGFRvIII), 75 impaired downregulation of the EGFR, 76 and gene amplification of the EGFR loci.…”

Section: The Role Of Egfr In Human Cancersmentioning

confidence: 99%

Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab

Brand

Iida

Wheeler

2011

Cancer Biology & Therapy

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191

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The epidermal growth factor receptor (eGFR) is a receptor tyrosine kinase belonging to the HeR family of receptor tyrosine kinases. Receptor activation upon ligand binding leads to down stream activation of the Pi3K/AKT, RAs/RAF/MeK/ eRK and PLCγ/PKC pathways that influence cell proliferation, survival and the metastatic potential of tumor cells. increased activation by gene amplification, protein overexpression or mutations of the eGFR has been identified as an etiological factor in a number of human epithelial cancers (e.g., NsCLC, CRC, glioblastoma and breast cancer). Therefore, targeting the eGFR has been intensely pursued as a cancer treatment strategy over the last two decades. To date, five eGFR inhibitors, including three small molecule tyrosine kinase inhibitors (TKis) and two monoclonal antibodies have gained FdA approval for use in oncology. Both approaches to targeting the eGFR have shown clinical promise and the anti-eGFR antibody cetuximab is used to treat HNsCC and CRC. despite clinical gains arising from use of cetuximab, both intrinsic resistance and the development of acquired resistance are now well recognized. in this review we focus on the biology of the eGFR, the role of eGFR in human cancer, the development of

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“…Similar controversies exist regarding the clinical relevance of the epidermal growth factor receptor (EGFR) in EC in general and more specifically in type II EC. EGFR expression has been demonstrated in 43 -67% of patients with endometrial cancer and its association with clinical outcome has been explored with some studies demonstrating an association between EGFR expression and poor clinical outcome (Khalifa et al, 1994;Scambia et al, 1994;Niikura et al, 1995) whereas others show no association (Reinartz et al, 1994). Moreover, the clinical role of EGFR expression specifically in type II EC has not yet been studied.…”

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confidence: 99%

HER2 gene amplification and EGFR expression in a large cohort of surgically staged patients with nonendometrioid (type II) endometrial cancer

et al. 2008

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Type II endometrial cancers (uterine serous papillary and clear cell histologies) represent rare but highly aggressive variants of endometrial cancer (EC). HER2 and EGFR may be differentially expressed in type II EC. Here, we evaluate the clinical role of HER2 and EGFR in a large cohort of surgically staged patients with type II (nonendometrioid) EC and compare the findings with those seen in a representative cohort of type I (endometrioid) EC. In this study HER2 gene amplification was studied by fluorescence in situ hybridisation (FISH) and EGFR expression by immunohistochemistry. Tissue microarrays were constructed from 279 patients with EC (145 patients with type I and 134 patients with type II EC). All patients were completely surgically staged and long-term clinical follow up was available for 258 patients. The rate of HER2 gene amplification was significantly higher in type II EC compared with type I EC (17 vs 1%, Po0.001). HER2 gene amplification was detected in 17 and 16% of the cases with uterine serous papillary and clear cell type histology, respectively. In contrast, EGFR expression was significantly lower in type II compared with type I EC (34 vs 46%, P ¼ 0.041). EGFR expression but not HER2 gene amplification was significantly associated with poor overall survival in patients with type II EC, (EGFR, median survival 20 vs 33 months, P ¼ 0.028; HER2, median survival 18 vs 29 months, P ¼ 0.113) and EGFR expression retained prognostic independence when adjusting for histology, stage, grade, and age (EGFR, P ¼ 0.0197; HER2, P ¼ 0.7855). We conclude that assessment of HER2 gene amplification and/or EGFR expression may help to select type II EC patients who could benefit from therapeutic strategies targeting both HER2 and EGFR.

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Significance of epidermal growth factor receptor expression in primary human endometrial cancer

Cited by 52 publications

References 21 publications

Expression Density of Receptors as a Potent Regulator of Cell Function and Property in Health and Pathology

Expression Density of Receptors as a Potent Regulator of Cell Function and Property in Health and Pathology

Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab

HER2 gene amplification and EGFR expression in a large cohort of surgically staged patients with nonendometrioid (type II) endometrial cancer

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