SEARCH · PubMed Health

Results for “EGFR”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2025

Implications of EGFR expression on EGFR signaling dependency and adaptive immunity against EGFR-mutated lung adenocarcinoma.

BACKGROUND: In EGFR-mutated lung adenocarcinoma (EGFRm LUAD), EGFR mutations do not necessarily result in increased EGFR expression (EGFR-exp), which differs among patients. However, the factors influencing EGFR-exp and the impact of EGFR-exp on tumor characteristics in patients with EGFRm LUAD remain unclear. PATIENTS AND METHODS: Whole-exome and RNA sequencing were performed for patients with early- and advanced-stage EGFRm LUAD. The patients were classified into low or high EGFR-exp groups based on the median transcripts per million. We retrospectively examined the association between EGFR-exp, genomic characteristics, downstream EGFR signaling activity, tumor microenvironment (TME) status, and clinical outcomes. RESULTS: This study included 450 and 45 patients in the early- and advanced-stage cohorts, respectively. In both cohorts, the EGFR-exp low group exhibited a lower incidence of TP53 co-mutations and EGFR amplification and a higher incidence of EGFR subclonal mutations than the EGFR-exp high group. Furthermore, downstream EGFR signaling pathways, such as the MAPK signaling, were less activated in the EGFR-exp low group. However, this group showed significantly enriched adaptive immune response pathways (Q < 0.0001) and an immune-inflamed TME. Additionally, a low EGFR-exp was a significantly favorable factor for postoperative relapse (odds ratio [OR], 0.6; P = 0.04). However, in the advanced-stage cohort, a low EGFR-exp was a significant risk factor for non-responders to osimertinib (OR, 17.5; P = 0.03). CONCLUSIONS: In EGFRm LUAD, significant associations were observed between EGFR-exp levels and both EGFR signaling pathways and adaptive immune status, which in turn influence clinical outcomes. This large-scale multi-omics analysis highlights the heterogeneity among patients with EGFRm LUAD and emphasizes the need to assess EGFR-exp levels alongside mutation status for optimal treatment strategies in EGFRm LUAD.

Humans↗

PubMed2026

Novel Co-Occurrence of Germline EGFR p.V843I and Somatic EGFR Exon 19 Deletion in NSCLC: Insights into Reduced Sensitivity to EGFR-TKIs.

Germline EGFR pathogenic variants (PVs) are rare and define a distinct hereditary subset of NSCLC with unique clinical characteristics. Germline EGFR p.T790M is the most frequent and best characterized, with reported sensitivity to first- and second-generation EGFR-TKIs. Yet, the response of germline EGFR variants, especially the rarer ones such as p.V843I, to osimertinib remains poorly characterized. Given the very low frequency of germline non-p.T790M variants, their clinical relevance can only be investigated via case reports. Herein, we report what is, to the best of our knowledge, the first case of advanced lung adenocarcinoma harboring a germline EGFR p.V843I variant coexisting in cis with the unusual somatic EGFR exon 19 C-helix deletion, p.S752_I759del. Additionally, a somatic TP53 variant was detected. Treatment with afatinib induced a partial response lasting only six months, as rapid disease progression occurred without identifiable acquired resistance mechanisms. Subsequently, no objective response to osimertinib or afatinib rechallenge was observed. Acquired EGFR and MET amplification were detected in corresponding rebiopsies. Overall survival was 29 months. Our findings suggest that, despite the presence of the previously reported EGFR-TKI-sensitive, EGFR p.S752_I759del, the co-occurrence of germline p.V843I may have contributed to reduced sensitivity to afatinib and osimertinib. This case expands the molecular spectrum of hereditary EGFR-mutated NSCLC and, together with our narrative review of the literature, supports an emerging model in which germline EGFR PVs may act both as tumor-predisposing events and as potential mechanisms of early resistance to EGFR-TKIs.

Humans↗

PubMed2025

Efficacy of EGFR tyrosine kinase inhibitors in patients with non-small cell lung cancer with EGFR exon 19 insertions: clinical-genomic, preclinical analysis through LC-SCRUM-Asia (multi-institutional genomic screening registry).

BACKGROUND: EGFR exon 19 insertions (EGFRex19ins) are rare EGFR mutations. Their clinical-genomic characteristics and outcomes with EGFR-tyrosine kinase inhibitors (TKIs) remain uncertain. METHODS: We evaluated the clinical-genomic characteristics and outcomes of EGFR-TKIs for EGFRex19ins in the multi-institutional prospective lung cancer genomic screening project (LC-SCRUM-Asia). We also studied preclinical Ba/F3 models expressing EGFR-K745_E746insIPVAIK (Ba/F3-IPVAIK) to investigate their sensitivity to 1st-, 2nd-, 3rd-generation, and EGFR exon 20 insertion-active TKIs. RESULTS: In LC-SCRUM-Asia, 16,204 NSCLC patients were enrolled from March 2015 to December 2023. EGFRex19ins were detected in 13 samples (0.1 % of NSCLC). The median age was 72 years (range, 38-80); most patients were female (77 %), had adenocarcinoma (92 %), and were never-smokers (62 %). Twelve patients (93 %) had EGFR-K745_E746insIPVAIK, while one (7 %) had EGFR-K745_E746insVPVAIK. The most frequent co-mutation was TP53 (62 %); no patients had other driver alterations. Six patients (46 %) tested positive for EGFR exon 19 deletions with PCR-based Cobas EGFR test, likely due to cross-reactivity arising from sequence homology. Twelve patients received EGFR-TKIs; five (42 %) experienced partial response. In the preclinical study, Ba/F3-IPVAIK showed the highest sensitivity to 2nd-generation EGFR-TKIs compared to other EGFR-TKIs. Structural studies supported these consistent results. When broken down by EGFR-TKI generations, response rates for 1st-, 2nd-, and 3rd-generation TKIs were 50 % (1/2), 80 % (4/5), and 0 % (0/5), respectively. The median PFS for 1st-, 2nd-, and 3rd-generation TKIs were 8.7 (95 % CI, 7.4-NR), 14.7 (95 % CI, 8.0-NR), and 4.4 (95 % CI, 3.4-NR) months, respectively. CONCLUSION: Our preclinical, structural, and clinical findings indicate 2nd-generation EGFR-TKIs are more effective for EGFRex19ins compared to other TKIs.

Adult↗

PubMed1994

Emergence of MCF-7 cells overexpressing a transfected epidermal growth factor receptor (EGFR) under estrogen-depleted conditions: evidence for a role of EGFR in breast cancer growth and progression.

Overexpression of epidermal growth factor receptor (EGFR) is correlated with loss of estrogen receptor and poor prognosis in breast cancer. To investigate this phenomenon, we transfected a cytomegalovirus expression vector directing the expression of EGFR into estrogen receptor-positive MCF-7 breast cancer cells and into a clone of MCF-7 cells previously transfected with transforming growth factor alpha. Cells arising from single clones or pooled polyclonal populations maintained in charcoal-stripped calf serum, a medium devoid of estrogen, overexpressed EGFR. Switching these cells to a medium containing fetal calf serum or charcoal-stripped calf serum plus 17 beta-estradiol resulted in the emergence of a population expressing low EGFR levels. Loss of expression was not a consequence of nonspecific repression of the cytomegalovirus promoter, because expression of the fibroblast growth factor (FGF)-4 complementary DNA in a similar vector was not lost in fetal calf serum. While loss of EGFR overexpression in fetal calf serum was seen at both the protein and mRNA levels, Southern blotting shows that this was not due to loss of the transfected gene. Subclones of a cell population with low EGFR expression were capable of increasing expression upon estrogen withdrawal, demonstrating that the changes in EGFR expression were reversible and suggesting a growth advantage conferred by EGFR overexpression under these restrictive growth conditions. Overexpression of EGFR did not result in loss of ER expression. These results suggest a role for overexpression of EGFR in the growth of estrogen receptor-positive breast cancer cells in the absence of estrogen.

Animals↗

PubMed2026

Enozertinib Is a Selective, Brain-Penetrant EGFR Inhibitor for Treating Non-Small Cell Lung Cancers with EGFR Exon 20 and Atypical Mutations.

UNLABELLED: EGFR mutations are common oncogenic drivers in non-small cell lung cancer (NSCLC), and approximately half of patients develop brain metastases over the course of their disease. Patients with nonclassic EGFR mutations, such as insertions in exon 20, are a high unmet need with a worse prognosis compared with patients with classic EGFR mutations. Here, we describe the discovery and development of enozertinib (formerly ORIC-114), a highly brain-penetrant, orally bioavailable, irreversible inhibitor that targets EGFR exon 20 mutations with unparalleled kinome selectivity. Preclinical studies revealed strong potency and tumor regressions driven by enozertinib across a broad range of atypical EGFR-mutant models. In a phase I clinical trial of enozertinib in patients with advanced NSCLC bearing atypical mutations in EGFR, a patient harboring an EGFR exon 20 insertion experienced sustained complete response of all systemic and brain metastases. Together, these findings identify enozertinib as a promising investigational inhibitor to address the unmet need for brain-penetrant therapies in NSCLC with EGFR exon 20 insertions or other atypical mutations. SIGNIFICANCE: Preclinical and initial phase I clinical data demonstrate the potency, kinome selectivity, efficacy, and brain penetration of enozertinib in NSCLC with EGFR exon 20 insertions and atypical mutations, warranting further clinical development.

Carcinoma, Non-Small-Cell Lung↗

PubMed2026

Targeting EGFR-Mutant Non-Small Cell Lung Cancer in Asia: An Update on Monotherapy and Combination Therapy With EGFR Inhibitors.

EGFR-mutant lung cancer represents a major subtype of non-small cell lung cancer in Asia, with particularly high prevalence in never-smokers, women, and patients with adenocarcinoma histology. Although this clinicopathologic enrichment has been recognized for more than two decades, the mechanisms underlying the excess frequency of EGFR-mutant disease in Asian populations remain only partially understood. Accumulating evidence suggests a multifactorial basis involving host genetic susceptibility and diversity, endogenous mutational processes and exogenous exposures such as ambient particulate matter. In particular, recent genomic and experimental studies support a tumour-promotion framework in which inflammatory microenvironmental cues may facilitate the outgrowth of pre-existing oncogenic clones, while mutational signatures provide genomic footprints of these processes. In parallel, the treatment landscape for EGFR-mutant non-small cell lung cancer has evolved substantially with successive generations of EGFR tyrosine kinase inhibitors (EGFR-TKIs), leading to marked improvements in survival. However, acquired resistance remains inevitable in most patients with advanced disease and is driven by both genetic and non-genetic mechanisms, including secondary EGFR alterations, bypass pathway activation, TP53-associated genomic instability, adaptive mutagenesis, and drug-tolerant persister states. These insights have provided a strong rationale for combination strategies beyond EGFR-TKI monotherapy. In this review, we summarize current understanding of the epidemiology and biological basis of EGFR-mutant lung cancer in Asia and discuss the preclinical rationale and emerging clinical evidence supporting combination approaches with chemotherapy, anti-angiogenic agents, and EGFR/MET-directed therapies.

EGFR mutations↗

PubMed2026

Ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with advanced EGFR-mutated non-small-cell lung cancer after disease progression on EGFR tyrosine kinase inhibitor therapy (HARMONi): a multicentre, randomised, double-blind, phase 3 trial.

BACKGROUND: Ivonescimab has shown clinical efficacy in non-small-cell lung cancer (NSCLC). We aimed to assess the efficacy and safety of ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with advanced EGFR-mutated NSCLC whose disease progressed after third-generation EGFR tyrosine kinase inhibitor (TKI) therapy. METHODS: HARMONi is a randomised, placebo-controlled, double-blind, phase 3 trial done at 114 cancer centres and hospitals across Asia, Europe, and North America. Eligible patients were aged at least 18 years (upper limit: 75 years in Asia) with stage IIIB/IIIC or IV non-squamous EGFR-mutated NSCLC, disease progression after treatment with a third-generation EGFR-TKI, and an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients were randomly assigned (1:1) via a centralised interactive voice response system or interactive web response system to receive ivonescimab (20 mg/kg) or placebo plus pemetrexed (500 mg/m2) and carboplatin (target area under the curve 5 mg/mL per min) intravenously every 3 weeks. Randomisation was stratified by brain metastases status at enrolment and geographical region. The primary endpoints were progression-free survival by blinded independent radiology review committee and overall survival in the intention-to-treat population. Safety was assessed in patients who received at least one dose of trial treatment. This study is registered with ClinicalTrials.gov (NCT06396065), has completed enrolment, and is ongoing for treatment and follow-up. FINDINGS: From Jan 25, 2022, to Oct 1, 2024, 660 individuals were screened for eligibility; of these, 438 were enrolled and randomly assigned to receive ivonescimab plus chemotherapy or placebo plus chemotherapy (219 per group). Of enrolled patients, 257 (59%) were female and 181 (41%) were male; 306 (70%) reported race as Asian, and 105 (24%) as White. At a median follow-up of 22·3 months (95% CI 21·5-23·0), 275 progression or death events had occurred in 345 patients (129 events among 172 patients in the ivonescimab plus chemotherapy group and 146 events among 173 patients in the placebo plus chemotherapy group). Median progression-free survival was 6·8 months (95% CI 5·7-7·1) in the ivonescimab plus chemotherapy group versus 4·4 months (4·1-5·5) in the placebo plus chemotherapy group (hazard ratio [HR] 0·52; 95% CI 0·41-0·66; p<0·0001). At a median follow-up of 29·7 months (95% CI 27·7-31·0), 262 deaths occurred in 438 patients (122 in the ivonescimab plus chemotherapy group and 140 in the placebo plus chemotherapy group). Median overall survival was 16·8 months (14·3-19·0) in the ivonescimab plus chemotherapy group versus 14·0 months (12·8-15·7) in the placebo plus chemotherapy group (HR 0·79; 0·62-1·01). The most common grade 3-4 treatment-related adverse events in the ivonescimab plus chemotherapy versus the placebo plus chemotherapy group were decreased neutrophil count (42 [19%] of 218 vs 36 [17%] of 218), decreased white blood cell count (28 [13%] vs 24 [11%]), decreased platelet count (27 [12%] vs 14 [6%]), and anaemia (22 [10%] vs 27 [12%]). Serious treatment-related adverse events occurred in 61 (28%) patients in the ivonescimab plus chemotherapy group and 33 (15%) patients in the placebo plus chemotherapy group. Treatment-related adverse events led to death in four patients (disease progression, multiple organ dysfunction syndrome, and hepatic failure, each in one patient; gastrointestinal haemorrhage and pulmonary embolism in one patient) in the ivonescimab plus chemotherapy group and five patients (pneumonitis, myocardial infarction, cerebrovascular accident, cognitive disorder, and embolic stroke, each in one patient) in the placebo plus chemotherapy group. INTERPRETATION: Ivonescimab plus chemotherapy showed a clinically meaningful and statistically significant progression-free survival benefit in patients with EGFR-mutated NSCLC after progression on EGFR-TKI therapy. The clinical benefit and lack of new safety signals of ivonescimab with chemotherapy support the potential for the combination as a new treatment option in this patient population. FUNDING: Summit Therapeutics.

Humans↗

PubMed1992

Colocalization of transforming growth factor-alpha and a functional epidermal growth factor receptor (EGFR) to the inner cell mass and preferential localization of the EGFR on the basolateral surface of the trophectoderm in the mouse blastocyst.

Results of previous studies suggested that responses of mouse blastocysts to TGF-alpha/EGF treatment are mediated by EGF receptors (EGFR) located on the apical surface of the trophectoderm (TE). We report here results of experiments using gold-labeled EGF that confirm the presence of these apically located EGFRs. In addition, immunoelectron microscopy (IEM) studies using anti-EGFR antibodies indicate that the receptor is preferentially distributed on the basolateral surface of the TE. Furthermore, the receptor is also present on the inner cell mass (ICM) and is likely to be functional, since treatment of isolated ICMs with TGF-alpha affects [35S]methionine uptake and incorporation into acid-insoluble material. IEM was also used to demonstrate that EGF, which is not synthesized by the mouse preimplantation embryo, is present in both the oviduct and the uterus. Maternally derived EGF is present in both ICM and TE cells in freshly isolated blastocysts, but is present in greatly reduced amounts following overnight culture of blastocysts in vitro. Last, IEM was also used to demonstrate that TGF-alpha is preferentially localized to the ICM and polar TE. The co-localization of TGF-alpha and functional EGFRs to the ICM and polar TE suggests potential autocrine, juxtacrine, and paracrine roles for TGF-alpha in blastocyst development.

Amino Acids↗

PubMed1994

Selective toxicity of TGF-alpha-PE40 to EGFR-positive cell lines: selective protection of low EGFR-expressing cell lines by EGF.

The sensitivity of human breast and lung cancer cell lines to TGF-alpha-PE40, a novel chimeric recombinant cytotoxin composed of two independent domains, (i) TGF-alpha and (ii) a 40 kDa segment of the Pseudomonas exotoxin protein, PE-40, was investigated. Toxicity varied widely, correlated with epidermal growth factor receptor (EGFR) levels (P = 0.01) and was greatly reduced by EGF, indicating that binding of TGF-alpha-PE40 to EGFR is important in mediating toxicity. Cell lines expressing low EGFR levels were most highly protected by EGF, indicating that normal (low EGFR-expressing) tissue may be selectively protected by EGF in vivo. P-glycoprotein did not confer resistance to TGF-alpha-PE40, and toxicity was unaffected by multidrug resistance-modulating agents (cyclosporin A, tamoxifen, verapamil), indicating a role for TGF-alpha-PE40 in the clinical management of drug-resistant tumours.

Breast Neoplasms↗

PubMed2026

EGFR-co-amplified lncRNA ELDR drives glioblastoma tumorigenicity by enhancing BMI1 activity.

BACKGROUND: In glioblastoma (GBM), epidermal growth factor receptor (EGFR) amplification, one of the most prevalent genetic alterations, often occurs on extrachromosomal DNAs (ecDNAs) that contain amplified oncogenes and regulatory elements, driving tumor progression. Despite the central oncogenic role of EGFR amplification, therapeutic strategies targeting EGFR have demonstrated limited clinical efficacy, suggesting that additional mechanisms may underlie EGFR-driven GBM malignancy and treatment resistance. Long non-coding RNAs (lncRNAs) are critical regulators in cancer; however, the roles of EGFR-associated lncRNAs-particularly those localized on ecDNA-in GBM tumorigenicity and therapeutic resistance remain poorly understood. METHODS: Transcriptomic and genomic analyses were performed to identify lncRNAs co-amplified with EGFR. Biochemical and molecular biological studies were carried out to reveal the mechanisms. In vivo xenograft models were used to evaluate the tumorigenicity and the therapeutic efficacy of combination treatment strategies. RESULTS: The lncRNA EGFR long non-coding downstream RNA (ELDR) was co-amplified with EGFR on ecDNA and chromosomes and was associated with poor prognosis in glioma. ELDR promoted GBM tumorigenicity through a BMI1-dependent epigenetic mechanism operating in parallel with canonical EGFR signaling. Mechanistically, ELDR interacted with purine-rich element-binding protein A (PURA), disrupted the inhibitory PURA-BMI1 interaction, and thereby enhanced the activity of BMI1, a core component of Polycomb repressive complex 1 (PRC1). Therapeutically, combining a BMI1 inhibitor or ELDR-targeting antisense oligonucleotides (ASOs) with an EGFR inhibitor erlotinib significantly enhanced antitumor efficacy in preclinical models of  EGFR  -amplified GBM with high ELDR expression. CONCLUSION: EGFR co-amplified ELDR promotes GBM tumorigenicity by enhancing BMI1 activity. Targeting the ELDR-BMI1 axis in combination with EGFR inhibition represents a promising therapeutic strategy for a subset of  EGFR  -amplified GBMs with high ELDR expression.

EGFR↗

PubMed2026

Spironolactone, early acute eGFR changes, and clinical outcomes in patients with heart failure with preserved ejection fraction: insights from TOPCAT Americas.

AIMS: Early acute changes in estimated glomerular filtration rate (eGFR) have been well described with renin-angiotensin system inhibitors and sodium-glucose cotransporter-2 inhibitors, but less is known about the frequency, prognostic relevance, and implications of these changes after mineralocorticoid receptor antagonist (MRA) initiation in patients with heart failure with preserved ejection fraction (HFpEF). METHODS: We performed a post-hoc analysis of 1648 patients enrolled in the TOPCAT trial (Americas regional subgroup), defining an early eGFR dip as a ≥15% decrease in eGFR between baseline and week 4. Landmark analyses assessed the association of eGFR changes, treatment, and the primary composite endpoint (cardiovascular death, HF hospitalization, or aborted cardiac arrest). RESULTS: Within 4 weeks of treatment initiation, 431 (26%) patients experienced acute eGFR decrease with a higher proportion of patients assigned to spironolactone [269 (33%)] compared with placebo [162 (20%)] (odds ratio 1.97; 95% confidence interval 1.58-2.47). An acute eGFR decrease was independently associated with higher risk of subsequent cardiovascular outcomes, irrespective of treatment arm. However, treatment with spironolactone appeared beneficial in reducing the primary cardiovascular outcome irrespective of the presence [hazard ratio 0.75 (0.53-1.08)] or absence [0.80 (0.64-1.00)] of early eGFR decrease (Pinteraction = .81). At any given magnitude of eGFR decline, risk of the primary endpoint was consistently lower with spironolactone compared with placebo (Pinteraction = .64). CONCLUSIONS: Early acute eGFR changes were common and adversely prognostic in patients with HFpEF. Spironolactone treatment was beneficial in improving cardiovascular outcomes, despite a modest increase in the likelihood of acute eGFR decrease. An acute eGFR decrease early after MRA initiation should not automatically prompt treatment discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00094302.

Humans↗

PubMed1988

Epidermal growth factor receptor (EGFr) status associated with failure of primary endocrine therapy in elderly postmenopausal patients with breast cancer.

We have used primary endocrine therapy for 61 elderly women with operable breast cancer (median age 77 years). Eleven patients (18%) had complete and 24 (39%) partial tumour regression, 12 (20%) had stable disease for a minimum of six months and 14 (23%) no response. Salvage surgery was undertaken in the 14 with no response and 8/9 with progressive disease following initial response, thus samples were available from relapse patients only. Assays for EGFr (two point radioreceptor assay) and oestrogen receptors (ER) (dextran coated charcoal method and an immunohistochemical method) were performed on 20/22 patients. Ten of these 20 tumours were EGFr+ (greater than 10 fmol mg-1 binding) and 9/13 patients progressing within six months had EGFr+ tumours. 15/22 were available for ER evaluation and there was no such association with ER status. EGFr status was also associated with early recurrence after surgery and death in the endocrine failure group (P less than 0.005 and P less than 0.05 respectively). Of a control population of 33 patients (median age 72 years) treated by primary surgery, only 6 were EGFr+. In this group early relapse was predicted by EGFr status, but not by ER status (median disease free survival for EGFr+ patients 15 months, and for EGFr- patients 40 months, P less than 0.01, logrank test). There was a significantly higher proportion of EGFr+ tumours in the endocrine failure group compared with the control population (P less than 0.001). EGFr status is a marker for rapid early progression on primary endocrine therapy and the development of non-excisional methods of EGFr analysis would allow better directed therapeutic decisions.

Aged↗

PubMed1995

[Oncogenes and cancer of the larynx. EGFR, p21 ras and HPV-DNA infections].

The modern concept of oncogenesis is based upon the interaction between factors which modulate cellular growth and differentiation, in particular oncogenes and tumor suppressor genes. The molecular events which induce laryngeal carcinogenesis are not yet known. Protoncogenes seem to be the target of the risk factors (cigarette smoking, alcohol abuse, ionizing radiations and, not least HPV-DNA) that are commonly considered related to laryngeal squamous cell carcinoma. New information on the role of alterations of oncogenes and/or their proteic products in laryngeal cancer will be useful in identifying new diagnostic and clinical therapeutical applications. The Authors investigated Epidermal Growth Factor Receptor (EGFR) expression in 103 primary laryngeal squamous cell carcinoma and 42 normal laryngeal tissue specimens in order to assess its clinical significance in primary laryngeal cancer. Significantly higher EGFR levels were found in cancer specimens compared with normal mucosa (p < 0.001). EGFR expression did not correlate with age, tumor localization, T classification, cervicallymphonode involvement or surgery, whereas in G3 tumors it was significantly higher than in G1-G2 (p < 0.05). Follow-up data were available for 74 cases: EGFR levels resulted significantly higher in patients who had a recurrence of the disease than those in recurrence-free patients (p < 0.05). The 24-month disease-free survival (DFS) was 58% for EGFR+ patients and 82% for EGFR-subjects. Multivariate analysis permitted identification of EGFR status and tumor localization as significant independent prognostic factors. Data reported here suggest that EGFR expression probably plays a role not only by regulating the growth of laryngeal cancer, but also by identifying a sub-set of laryngeal cancer patients at a higher degree of relapse risk and with an unfavorable prognosis. Furthermore, in this study p21-ras expression in 43 primary laryngeal cancers and in 7 normal laryngeal mucosa specimens was evaluated. Scattered p21 levels, expressed as optical density (O.D), were found in normal mucosa (median = 1.94) and in primary laryngeal tumours (median = 1.74). Higher p21 levels were found in neoplastic tissue than in normal laryngeal tissue (median = 2.54 vs median = 1.94; p = 0.023). The correlation between p21 ras protein and EGFR levels was also investigated. EGFR+ cases do not show any difference in p21 expression with respect to EGFR- cases (median = 1.52 O.D. vs median = 1.84). Our findings suggest that overexpression of p21 is associated with malignant phenotype in laryngeal cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed2026

Radiomics-based gradient boosting model on contrast-enhanced MRI for non-invasive prediction of epidermal growth factor receptor expression and therapeutic response to EGFR-targeted antibody-drug conjugates in high-grade glioma organoid models.

BACKGROUND: Epidermal growth factor (EGF) and its receptor EGF(EGFR) play crucial roles in glioblastoma (GBM) prognosis. However, non-invasive assessment of their expression remains challenging. This study aimed to determine whether radiomics features extracted from contrast-enhanced MRI could predict EGFR expression in high-grade gliomas (HGG) and to explore their associations with immune infiltration and therapeutic response of EGFR-Targeted antibody drug conjugates(EGFR-ADCs). METHODS: We extracted radiomic features from contrast-enhanced MRI of 298 GBM patients from The Cancer Imaging Archive (TCIA) and matched them with RNA-seq data from The Cancer Genome Atlas (TCGA). Feature selection was performed using minimum redundancy maximum relevance (mRMR) and recursive feature elimination (RFE). Machine learning models were built to predict EGF/EGFR expression. Radiogenomic associations were validated by immune infiltration analysis. Patient-Derived Tumor-Like Cell Clusters (PTC) were used to compare the antitumor efficacy of EGFR- ADCs and temozolomide. RESULTS: Elevated EGF/EGFR expression correlated with poor prognosis and increased infiltration of M2 macrophages, regulatory T cells, and CD4⁺ memory T cells. Pathway analysis demonstrated significant enrichment of the mechanistic target of rapamycin (mTOR) and Mitogen-Activated Protein Kinase (MAPK) signaling cascades. Radiomics-based prediction models achieved robust performance (AUC > 0.85) in stratifying EGFR expression status. In EGFR-positive tumor tissues, EGFR-ADCs exerted antitumor efficacy similar to that of temozolomide. CONCLUSIONS: EGF/EGFR expression is associated with immunosuppressive microenvironments and adverse outcomes in HGG. Radiomics may provide a non-invasive approach for estimating EGFR expression, although model performance requires external validation and EGFR-ADCs showed partial inhibitory activity within the tested range, though potency remains to be defined.These findings suggest a framework into radiogenomic stratification and targeted therapy in GBM.

Radiomics↗

PubMed1991

Epidermal growth factor receptor (EGFr); results of a 6 year follow-up study in operable breast cancer with emphasis on the node negative subgroup.

More accurate criteria are required for the selection of patients with node-negative breast cancer for systemic adjuvant therapy. Expression of epidermal growth factor receptor (EGFr) has been shown previously to be inversely related to oestrogen receptor (ER) in patients with operable breast cancer and to be associated with a poorer prognosis. Analysis of EGFr and ER was performed on tumour samples from 231 patients with operable breast cancer followed for up to 6 years after surgery. The median duration of follow-up in patients still alive at the time of analysis was 45 months. Thirty-five percent of patients (82) had tumours with greater than 10 fmol mg-1 I125-EGF binding (EGFr+) and 47% (109) and cystolic ER concentrations greater than 5 fmol mg-1 (ER+), with a marked inverse relationship between EGFr and ER (P less than 0.00001). In a univariate analysis EGFr was second only to axillary node status as a prognostic marker for all patients both in terms of relapse-free and overall survival (P less than 0.001, log rank). For patients with histologically negative axillary nodes EGFr was superior to ER in predicting relapse and survival (P less than 0.01 and P less than 0.005 respectively compared to P less than 0.1 and P less than 0.1, log rank). In a multivariate (Cox model) analysis only EGFr, out of EGFr, ER, size and grade, was predictive for either relapse-free or overall survival for patients with node-negative disease (P = 0.05 and P = 0.026 respectively). EGFr has been shown to be a marker of poor prognosis for patients with node-negative breast cancer. Since patients with EGFr+ tumours are unlikely to respond to hormone therapy it may be possible to select them for trials of systemic adjuvant chemotherapy.

Breast Neoplasms↗

PubMed1994

Expression of epidermal growth factor receptor (EGFr) immunoreactivity in human cutaneous nerves and sensory corpuscles.

BACKGROUND: The epidermal growth factor receptor (EGFr) binds both epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha), which are currently considered among putative growth factors playing a role in the nervous system. EGFr and their ligands have been localized in the mammalian peripheral nervous system. The present study was undertaken to investigate whether nerves and sensory corpuscles supplying human glabrous skin express EGFr. METHODS: Formaldehyde fixed, paraffin embedded samples of finger-tip digital skin obtained from adult healthy subjects were processed for indirect PAP immunohistochemistry using a monoclonal antibody against an epitope of the intracellular domain of EGFr. To ascertain the localization of EGFr immunoreactivity, neurofilament proteins (NFP), S100 protein (S100P), and epithelial membrane antigen (EMA) were studied in parallel to label axons, Schwann cells, and perineurial cells, respectively, as well as their corpuscular derivatives. RESULTS: A variable intensity of EGFr immunostaining was regularly observed in the perineurium and Schwann cells, and occasionally in the axons of nerve bundles. EGFr immunoreactivity was also present in the axon and lamellar cells of Meissner corpuscles, and within the axon, inner-core, outer-core, and capsule of Pacinian corpuscles. CONCLUSIONS: Present results demonstrate that human cutaneous nerves and sensory corpuscles express EGFr suggesting a role for peptides able to bind EGFr, i.e., EGF and TGF alpha, in the human peripheral nervous sensory system.

Adult↗

PubMed1993

In situ hybridization for epidermal growth factor receptor (EGFR) external domain transcripts in prostatic adenocarcinoma.

We examined prostatic adenocarcinomas from 19 formalin fixed radical prostatectomy specimens for EGFR by in situ hybridization employing a 24 base synthetic biotin-labeled oligonucleotide probe complementary to the 5' end of EGFR mRNA. All slides were examined by light microscopy using a 25x objective. Each field was given three values: 1) Gleason grade (1-5), 2) Nuclear grade [small (< 5.0 mu), intermediate (5-10 mu), large (> 10 mu)], and 3) EGFR staining intensity score (0, absent; 1, weak; 2+, moderate to strong). A total 851 25x fields of prostatic adenocarcinoma were studied. All cancers demonstrated at least some degree of cytoplasmic EGFR message. The EGFR intensity score correlated best with tumor nuclear size. No correlation with Gleason grade was observed. Cytoplasmic staining was also identified in the basal cell layer of benign glands, high grade prostatic intraepithelial neoplasia, stromal nodules, transitional epithelium, periurethral glands, and ganglion cells. Competitive hybridization experiments using an unlabeled EGFR probe showed markedly diminished hybridization signal, while in situ hybridization with a biotin-labeled EGFR sense probe was negative. Immunohistochemistry on 13 of the tumors with 2 monoclonal antibodies against EGFR showed staining in only 1/13 and 10/13 tumors. EGFR expression appears to be most prominent in tumors of high nuclear grade. Further studies will be necessary to explore this growth factor as a prognostic variable in this tumor.

Adenocarcinoma↗

PubMed1990

Epidermal growth factor receptor (EGFr) as a marker for poor prognosis in node-negative breast cancer patients: neu and tamoxifen failure.

Analysis of EGFr and ER was performed on tumour samples from 231 patients with operable breast cancer followed for up to 6 yr after surgery. The median duration of follow-up in patients still alive at the time of analysis was 45 months. Thirty-five percent of patients (82) had tumours greater than 10 fmol/mg 125I-EGF binding (EGFr+) and 47% (109) had cystolic ER concentration greater than 5 fmol/mg (ER+), with a marked inverse relationship between EGFr and ER (P less than 0.00001). EGFr was second only to axillary node status as a prognostic marker for all patients both in terms of relapse-free and overall survival (P less than 0.001, logrank EGFr+ vs EGFr-). For patients with histologically negative axillary nodes EGFr was superior to ER in predicting relapse and survival (P less than 0.01 and P less than 0.005, respectively, compared to P less than 0.1 and P less than 0.1, logrank). In a multivariate (Cox model) analysis only EGFr, out of EGFr, ER, size and grade, was predictive for either relapse-free or overall survival for patients with node-negative disease (P = 0.052 and P = 0.026, respectively). The correlation of neu expression with response to tamoxifen in patients with recurrent disease was assessed immunochemically. Response rate was reduced in the presence of neu from 50 to 17% for ER+ cases and from 26 to 0% for ER- cases.

Biomarkers, Tumor↗