Epidermal growth factor receptor expression correlates with poor prognosis in non-small cell lung cancer patients with p53 overexpression.

Ohsaki, Yoshinobu; Tanno, Satoshi; Fujita, Yuka; Toyoshima, Eri; Fujiuchi, Satoru; Nishigaki, Yutaka; Ishida, Sakae; Nagase, Atsushi; Miyokawa, Naoyuki; Hirata, Satoshi; Kikuchi, Kenjiro

doi:10.3892/or.7.3.603

Cited by 146 publications

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“…EGFR is known to activate MAPK superfamily, including the extracellular signal-regulated kinase (ERK). The ERK pathway, activated by mitogenic stimuli such as growth factors, cytokines, and phorbol esters, plays a major role in regulating lung adenocarcinoma cell growth, survival, and differentiation (14,(15)(16)(17)(18). The decreased expression of EGFR following MAG-DHA+CBT treatment observed herein is concomitant with a decrease in the phosphorylation of ERK and a reduced proliferation level.…”

Section: Effect Of Combined Mag-dha and Cbt Treatments On Egfr And Ermentioning

confidence: 99%

“…These mutations can result in constitutive activation of signal transduction pathways, leading to cell proliferation or anti-apoptosis, regardless the presence of extracellular ligand (15). Some studies have shown that EGFR expression in NSCLC is associated with reduced survival, frequent lymph node metastasis, and poor chemosensitivity (16)(17)(18). Upon binding of a specific ligand (epidermal growth factor, EGF), the normally functioning EGFR undergoes conformational change and phosphorylation of the intracellular domain occurs, leading to downstream signal transduction by various pathways (14).…”

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confidence: 99%

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Docosahexaenoic Acid Monoglyceride Increases Carboplatin Activity in Lung Cancer Models by Targeting EGFR

Morin¹,

Fortin

2017

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Abstract. Background Lung cancer is the leading cause of cancer mortality in North America with non-small cell lung cancer (NSCLC) accounting for over 75 % of lung cancer patients (1). Studies suggest that omega-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) display chemopreventive and therapeutic potential against lung cancer (2). Dietary intake of PUFAs is associated with a lower risk of developing cancer (3, 4), and inhibits both the growth and metastasis of animal tumors and xenografts (2-4).

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Section: Effect Of Combined Mag-dha and Cbt Treatments On Egfr And Ermentioning

confidence: 99%

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confidence: 99%

Docosahexaenoic Acid Monoglyceride Increases Carboplatin Activity in Lung Cancer Models by Targeting EGFR

Morin¹,

Fortin

2017

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“…[9][10][11] On the other hand, overexpression of EGFR was reported to be associated with lymph node involvement and poor prognosis in NSCLC. 11,12 Few investigations addressed the coexpression of E-cad and EGFR, 13 and the relation between this expression and patient survival in NSCLC. The aim of this study was to utilize a high-throughput tissue microarray (TMA) and immunohistochemistry (IHC) for assessment of E-cad and EGFR expressions in two major subtypes of NSCLC, adenocarcinoma (AdC) and squamous cell carcinoma (SCC), to evaluate their association with clinicopathologic variables and patient survival, and to address their possible value as prognosticators.…”

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confidence: 99%

Altered E-cadherin and epidermal growth factor receptor expressions are associated with patient survival in lung cancer: a study utilizing high-density tissue microarray and immunohistochemistry

et al. 2004

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E-cadherin (E-cad) and epidermal growth factor receptor (EGFR) are important cell adhesion and signaling pathway mediators. This study aimed to assess their expression in lung adenocarcinoma (AdC) and squamous cell carcinoma (SCC) and their association with clinicopathologic variables. In all, 130 resectable lung cancers (stages I-IIIA) were studied using a high-density tissue microarray. Two to three cores from each case were arrayed into three blocks using a Beecher system. Immunohistochemistry was performed using an avidinbiotin complex method and monoclonal antibodies against E-cad and EGFR. Unequivocal membrane staining in 410% of tumor cells was considered as a positive expression of E-cad and EGFR. Markers expression and coexpression were analyzed against clinicopathologic variables (age, gender, smoking status, performance status, weight loss, histology, grade, stage, and lymph node involvement) and patient survival. There were 118, 126, and 115 cases that were fully assessable for E-cad, EGFR, and both markers, respectively. For E-cad, 65 cases (55%) were positive ( þ ), 53 (45%) were negative (À); 23 cases of the negative group had only cytoplasmic staining. For EGRF, 43 cases (34%) were ( þ ), and 83 (66%) were (À). There was no significant association between E-cad or EGFR, and any of the clinicopathologic variables except for an association between EGFR( þ ) and SCC histologic type. Both negative and cytoplasmic staining of E-cad correlated with shorter patient survival with P ¼ 0.008 and 0.002, respectively. EGFR expression did not correlate with patient survival; however, patients with E-cad(À)/EGFR( þ ) phenotype had poorer survival than those with E-cad( þ )/EGFR(À) (P ¼ 0.026). Our study suggests that lung AdC and SCC may be stratified based on expression of E-cad and EGFR with the E-cad(À)/EGFR( þ ) expression having a worse disease outcome. Moreover, the cytoplasmic expression of E-cad may represent an altered localization of this protein in association with tumorigenicity.

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“…Immunohistochemical studies have reported EGFR overexpression in 22 -81% of NSCLC tumours depending on the antibody used and cut point that defines overexpression (Veale et al, 1987;Volm et al, 1993;Pfeiffer et al, 1996;Cornianu and Tudose, 1997;Pastorino et al, 1997;Rusch et al, 1997;Fontanini et al, 1998;Greatens et al, 1998;D'Amico et al, 1999;Fu et al, 1999;Cox et al, 2000;Ohsaki et al, 2000;Selvaggi et al, 2002;Hirsch et al, 2003;Kanematsu et al, 2003;Mukohara et al, 2003;Onn et al, 2003). The majority of these studies have failed to demonstrate an association with prognosis (Table 1).…”

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Coexpression of epidermal growth factor receptor with related factors is associated with a poor prognosis in non-small-cell lung cancer

2004

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The epidermal growth factor receptor (EGFR) is commonly expressed in non-small-cell lung cancer (NSCLC) and promotes a host of mechanisms involved in tumorigenesis. However, EGFR expression does not reliably predict prognosis or response to EGFR-targeted therapies. The data from two previous studies of a series of 181 consecutive surgically resected stage I -IIIA NSCLC patients who had survived in excess of 60 days were explored. Of these patients, tissue was available for evaluation of EGFR in 179 patients, carbonic anhydrase (CA) IX in 177 patients and matrix metalloproteinase-9 (MMP-9) in 169 patients. We have previously reported an association between EGFR expression and MMP-9 expression. We have also reported that MMP-9 (P ¼ 0.001) and perinuclear (p)CA IX (P ¼ 0.03) but not EGFR expression were associated with a poor prognosis. Perinuclear CA IX expression was also associated with EGFR expression (Po0.001). Multivariate analysis demonstrated that coexpression of MMP-9 with EGFR conferred a worse prognosis than the expression of MMP-9 alone (Po0.001) and coexpression of EGFR and pCA IX conferred a worse prognosis than pCA IX alone (P ¼ 0.05). A model was then developed where the study population was divided into three groups: group 1 had expression of EGFR without coexpression of MMP-9 or pCA IX (number ¼ 21); group 2 had no expression of EGFR (number ¼ 75); and group 3 had coexpression of EGFR with pCA IX or MMP-9 or both (number ¼ 70). Group 3 had a worse prognosis than either groups 1 or 2 (P ¼ 0.0003 and 0.027, respectively) and group 1 had a better prognosis than group 2 (P ¼ 0.036). These data identify two cohorts of EGFR-positive patients with diametrically opposite prognoses. The group expressing either EGFR and or both MMP-9 and pCA IX may identify a group of patients with activated EGFR, which is of clinical relevance with the advent of EGFR-targeted therapies.

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Epidermal growth factor receptor expression correlates with poor prognosis in non-small cell lung cancer patients with p53 overexpression.

Cited by 146 publications

References 0 publications

Docosahexaenoic Acid Monoglyceride Increases Carboplatin Activity in Lung Cancer Models by Targeting EGFR

Docosahexaenoic Acid Monoglyceride Increases Carboplatin Activity in Lung Cancer Models by Targeting EGFR

Altered E-cadherin and epidermal growth factor receptor expressions are associated with patient survival in lung cancer: a study utilizing high-density tissue microarray and immunohistochemistry

Coexpression of epidermal growth factor receptor with related factors is associated with a poor prognosis in non-small-cell lung cancer

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