Assessment of expression of epidermal growth factor receptor and p53 in meningiomas

Narla, Swetha; Uppin, Megha S; Saradhi, M Vijaya; Sahu, Barada Prasad; Purohit, A K; Challa, Sundaram

doi:10.4103/0028-3886.128276

Cited by 15 publications

(15 citation statements)

References 22 publications

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“…Since normal meninges were EGFR immunonegative, our findings support a general upregulation of this receptor in meningioma tissue in accordance with previous results and other studies (Carroll et al, 1997; Di Carlo et al, 1992; Halper et al, 1999; Horsfall et al, 1989; Huisman et al, 1991; Johnson et al, 1994; Kuratsu et al, 1994; Laurendeau et al, 2009; Lusis, Chicoine & Perry, 2005; Maiuri et al, 2007; Narla et al, 2014; Reubi et al, 1989; Torp et al, 1992). These findings are also supported by studies in which EGFR expression in meningiomas was determined by other techniques such as Northern and western blots, polymerase chain reactions (PCR) and ligand-binding studies (Andersson et al, 2004; Carroll et al, 1997; Guillaudeau et al, 2012; Kurihara et al, 1989; Laurendeau et al, 2009; Torp et al, 1992; Weisman, Raguet & Kelly, 1987).…”

Section: Discussionsupporting

confidence: 93%

“…In their study, Hilton et al found significantly higher expression of phosphorylated EGFR in tumor tissues compared with non-neoplastic tissues, and high expression of downstream signaling molecules (Hilton et al, 2016). The literature is conflicting concerning EGFR and malignancy, as some have found that high expression is positively related to tumor grade (Caltabiano et al, 2013; Diedrich et al, 1995; Halper et al, 1999) whereas others have found the opposite or no differences (Baxter et al, 2014; Guillaudeau et al, 2012; Jones et al, 1990; Kuratsu et al, 1994; Narla et al, 2014; Wernicke et al, 2010). However, these previous studies have not investigated the activated receptor.…”

Section: Discussionmentioning

confidence: 99%

“…EGFR and the ligands EGF and TGFα have been shown to be overexpressed in human meningiomas (Andersson et al, 2004; Baxter et al, 2014; Caltabiano et al, 2013; Camby et al, 1997; Carroll et al, 1997; Diedrich et al, 1995; Guillaudeau et al, 2012; Halper et al, 1999; Johnson et al, 1994; Kuratsu et al, 1994; Laurendeau et al, 2009; Lusis, Chicoine & Perry, 2005; Maiuri et al, 2007; Narla et al, 2014; Reubi et al, 1989; Torp et al, 1992; Wernicke et al, 2010), whereas non-neoplastic meningeal tissue show sparse or no reactivity (Carroll et al, 1997; Johnson et al, 1994; Torp et al, 1992), indicating a potential tumorigenic role of EGFR in these tumors. Both membranous and cytoplasmic EGFR immunoreactivity have been described in meningiomas (Guillaudeau et al, 2012; Halper et al, 1999; Horsfall et al, 1989; Johnson et al, 1994; Jones et al, 1990; Smith et al, 2007; Torp et al, 1992), however, the prognostic relevance is scarcely described (Guillaudeau et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…The receptor also seems to be activated (phosphorylated) (Carroll et al, 1997; Hilton et al, 2016). Moreover, the literature is conflicting regarding expression levels of EGFR across malignancy grades, as some report increasing expression with higher grades (Caltabiano et al, 2013; Diedrich et al, 1995; Halper et al, 1999) and others the opposite or no connection at all (Baxter et al, 2014; Guillaudeau et al, 2012; Jones et al, 1990; Kuratsu et al, 1994; Narla et al, 2014; Wernicke et al, 2010). Furthermore, the prognostic value of expression of either the intracellular or extracellular domain of the receptor is uncertain (Guillaudeau et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Expression and clinical value of EGFR in human meningiomas

Arnli

Backer-Grøndahl

Ytterhus

et al. 2017

PeerJ

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BackgroundMeningiomas are common intracranial tumors in humans that frequently recur despite having a predominantly benign nature. Even though these tumors have been shown to commonly express EGFR/c-erbB1 (epidermal growth factor receptor), results from previous studies are uncertain regarding the expression of either intracellular or extracellular domains, cellular localization, activation state, relations to malignancy grade, and prognosis.AimsThis study was designed to investigate the expression of the intracellular and extracellular domains of EGFR and of the activated receptor as well as its ligands EGF and TGFα in a large series of meningiomas with long follow-up data, and investigate if there exists an association between antibody expression and clinical and histological data.MethodsA series of 186 meningiomas consecutively operated within a 10-year period was included. Tissue microarrays were constructed and immunohistochemically analyzed with antibodies targeting intracellular and extracellular domains of EGFR, phosphorylated receptor, and EGF and TGFα. Expression levels were recorded as a staining index (SI).ResultsPositive immunoreactivity was observed for all antibodies in most cases. There was in general high SIs for the intracellular domain of EGFR, phosphorylated EGFR, EGF, and TGFα but lower for the extracellular domain. Normal meninges were negative for all antibodies. Higher SIs for the phosphorylated EGFR were observed in grade II tumors compared with grade I (p = 0.018). Survival or recurrence was significantly decreased in the time to recurrence analysis (TTR) with high SI-scores of the extracellular domain in a univariable survival analysis (HR 1.152, CI (1.036–1.280, p = 0.009)). This was not significant in a multivariable analysis. Expression of the other antigens did not affect survival.ConclusionEGFR is overexpressed and in an activated state in human meningiomas. High levels of ligands also support this growth factor receptor system to be involved in meningioma tumorigenesis. EGFR may be a potential candidate for targeted therapy.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression and clinical value of EGFR in human meningiomas

Arnli

Backer-Grøndahl

Ytterhus

et al. 2017

PeerJ

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show abstract

“…EGFR and the ligands EGF and TGFα have been shown to be overexpressed in human meningiomas (Andersson et al 2004;Baxter et al 2014;Caltabiano et al 2013;Camby et al 1997;Carroll et al 1997;Diedrich et al 1995;Guillaudeau et al 2012;Halper et al 1999;Johnson et al 1994;Kuratsu et al 1994;Laurendeau et al 2009;Lusis et al 2005;Maiuri et al 2007;Narla et al 2014;Reubi et al 1989;Torp et al 1992;Wernicke et al 2010), whereas nonneoplastic meningeal tissue show sparse or no reactivity (Carroll et al 1997;Johnson et al 1994;Torp et al 1992), indicating a potential tumorigenic role of EGFR in these tumors Both membranous and cytoplasmic EGFR immunoreactivity have been described in meningiomas (Guillaudeau et al 2012;Halper et al 1999;Horsfall et al 1989;Johnson et al 1994;Jones et al 1990; Smith et al 2007;Torp et al 1992), however, the prognostic relevance is scarcely described (Guillaudeau et al 2012). The receptor also seems to be activated (phosphorylated) PeerJ reviewing PDF | (2016:10:14229:2:0:NEW 27 Feb 2017)…”

Section: Introductionmentioning

confidence: 99%

Peer Review #2 of "Expression and clinical value of EGFR in human meningiomas (v0.1)"

2017

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Background: Meningiomas are common intracranial tumors in humans that frequently recur despite having a predominantly benign nature. Even though these tumors have been shown to commonly express EGFR/c-erbB1 (epidermal growth factor receptor), results from previous studies are uncertain regarding the expression of either intracellular or extracellular domains, cellular localization, activation state, relations to malignancy grade, and prognosis. Aims: This study was designed to investigate the expression of the intracellular and extracellular domains of EGFR and of the activated receptor as well as its ligands EGF and TGFα in a large series of meningiomas with long follow-up data, and investigate if there exists an association between antibody expression and clinical and histological data. Methods: A series of 186 meningiomas consecutively operated within a 10-year period was included. Tissue microarrays were constructed and immunohistochemically analyzed with antibodies targeting intracellular and extracellular domains of EGFR, phosphorylated receptor, and EGF and TGFα. Expression levels were recorded as a staining index (SI). Results: Positive immunoreactivity was observed for all antibodies in most cases. There was in general high SIs for the intracellular domain of EGFR, phosphorylated EGFR, EGF, and TGFα but lower for the extracellular domain. Normal meninges were negative for all antibodies. Higher SIs for the phosphorylated EGFR were observed in grade II tumors compared with grade I (p=0.018). Survival or recurrence was significantly decreased in the time to recurrence analysis (TTR) with high SI-scores of the extracellular domain in a univariable survival analysis (HR 1.152, CI (1.036 to 1.280, p=0.009)). This was not significant in a multivariable analysis. Expression of the other antigens did not affect survival. Conclusion: EGFR is overexpressed and in an activated state in human meningiomas. High levels of ligands also support this growth factor

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Zinc and zinc-containing biomolecules in childhood brain tumors

et al. 2016

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Zinc ions are essential cofactors of a wide range of enzymes, transcription factors, and other regulatory proteins. Moreover, zinc is also involved in cellular signaling and enzymes inhibition. Zinc dysregulation, deficiency, over-supply, and imbalance in zinc ion transporters regulation are connected with various diseases including cancer. A zinc ion pool is maintained by two types of proteins: (i) zinc-binding proteins, which act as a buffer and intracellular donors of zinc and (ii) zinc transporters responsible for zinc fluxes into/from cells and organelles. The decreased serum zinc ion levels have been identified in patients suffering from various cancer diseases, including head and neck tumors and breast, prostate, liver, and lung cancer. On the contrary, increased zinc ion levels have been found in breast cancer and other malignant tissues. Zinc metalloproteomes of a majority of tumors including brain ones are still not yet fully understood. Current knowledge show that zinc ion levels and detection of certain zinc-containing proteins may be utilized for diagnostic and prognostic purposes. In addition, these proteins can also be promising therapeutic targets. The aim of the present work is an overview of the importance of zinc ions, zinc transporters, and zinc-containing proteins in brain tumors, which are, after leukemia, the second most common type of childhood cancer and the second leading cause of death in children after accidents.

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Assessment of expression of epidermal growth factor receptor and p53 in meningiomas

Abstract: EGFR expression and Ki67 LI correlated with grade of meningioma P < 0.0001 and P < 0.0001 respectively which were statistically significant whereas p53 expression did not correlate (P - 0.90).

Cited by 15 publications

References 22 publications

Expression and clinical value of EGFR in human meningiomas

Expression and clinical value of EGFR in human meningiomas

Peer Review #2 of "Expression and clinical value of EGFR in human meningiomas (v0.1)"

Zinc and zinc-containing biomolecules in childhood brain tumors

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