BACKGROUND: At present, the research progress of targeted therapy for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene mutations in lung adenocarcinoma is very rapid, which brings new hope for the treatment of advanced lung adenocarcinoma patients. However, the specific imaging and pathological features of EGFR and ALK gene mutations in adenocarcinoma are still controversial. This study will further explore the correlation between EGFR, ALK gene mutations and imaging and pathological features in invasive lung adenocarcinoma. METHODS: A total of 525 patients with lung adenocarcinoma who underwent surgery in our center from January 2018 to December 2019 were included. According to the results of postoperative gene detection, the patients were divided into EGFR gene mutation group, ALK gene mutation group and wild group, and the EGFR gene mutation group was divided into exon 19 and exon 21 subtypes. The pathological features of the mutation group and wild group, such as histological subtype, lymph node metastasis, visceral pleural invasion (VPI) and imaging features such as tumor diameter, consolidation tumor ratio (CTR), lobulation sign, spiculation sign, pleural retraction sign, air bronchus sign and vacuole sign were analyzed by univariate analysis and multivariate Logistic regression analysis to explore whether the gene mutation group had specific manifestations. RESULTS: EGFR gene mutation group was common in women (OR=2.041, P=0.001), with more pleural traction sign (OR=1.506, P=0.042), and had little correlation with lymph node metastasis and VPI (P>0.05). Among them, exon 21 subtype was more common in older (OR=1.022, P=0.036), women (OR=2.010, P=0.007), and was associated with larger tumor diameter (OR=1.360, P=0.039) and pleural traction sign (OR=1.754, P=0.029). Exon 19 subtype was common in women (OR=2.230, P=0.009), with a high proportion of solid components (OR=1.589, P=0.047) and more lobulation sign (OR=2.762, P=0.026). ALK gene mutations were likely to occur in younger patients (OR=2.950, P=0.045), with somking history (OR=1.070, P=0.002), and there were more micropapillary components (OR=4.184, P=0.019) and VPI (OR=2.986, P=0.034) in pathology. CONCLUSIONS The EGFR and ALK genes mutated adenocarcinomas have specific imaging and clinicopathological features, and the mutations in exon 19 or exon 21 subtype have different imaging features, which is of great significance in guiding the clinical diagnosis and treatment of pulmonary nodules.
Adenocarcinoma of Lung/genetics* ; Aged ; Anaplastic Lymphoma Kinase/genetics* ; ErbB Receptors/genetics* ; Female ; Genes, erbB-1 ; Humans ; Lung Neoplasms/pathology* ; Mutation ; Tomography, X-Ray Computed/methods*

Lung cancer is the sixth leading cause of death worldwide and one of the leading cause of death from malignant tumors. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Epidermal growth factor receptor (EGFR) gene mutation is a common mutation in NSCLC. For advanced NSCLC patients with EGFR mutations, EGFR-tyrosine kinase inhibitors (EGFR-TKIs), such as Gefitinib, Afatinib, Oxitinib and other targeted therapies have become the first-line treatment recommended by many guidelines, but many patients develop acquired drug resistance after about 1 year of medication. Patients with drug resistance will have earlier disease progression than patients without drug resistance, which has an important impact on the prognosis of patients. At present, the main treatment for patients with acquired resistance is new target inhibition for resistant mutation. For example, if patients with T790M mutation are resistant to the first or second generation drugs such as Gefitinb and Afatinib, they can be treated with the third generation drugs (Osimertinib or Almonertinib), which can delay the progression of the disease. Therefore, the study of drug resistance mechanism and treatment of drug resistance patients are essential. This paper mainly reviews targeted therapy and drug resistance mechanism of EGFR-mutant NSCLC patients, in order to provide reference for clinical application of EGFR-TKIs.
.
Acrylamides ; Carcinoma, Non-Small-Cell Lung/pathology* ; Drug Resistance, Neoplasm/genetics* ; ErbB Receptors/genetics* ; Genes, erbB-1 ; Humans ; Indoles ; Lung Neoplasms/pathology* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Pyrimidines

OBJECTIVE: To explore the valuable predictors for evaluating progression-free survival (PFS) in patients with lung adenocarcinoma, we analyzed the potential roles of standardized uptake value (SUV)-derived parameters from ¹⁸F-FDG PET/CT, combining with the gene mutation states of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and other clinical characteristics. METHODS: Data of 84 lung adenocarcinoma patients pre-treated, who underwent ¹⁸F-FDG PET/CT scans, EGFR gene mutations test, ALK rearrangement assay and other relative tests, were retrospectively collected. Then a series of clinical parameters including EGFR/ALK mutation status and SUV-derived features [maximum standardized uptake value (SUVmax), average of standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] were evaluated. Best possible cutoff points for all measuring parameters were calculated using receiver operating characteristic curve (ROC) analysis. Survival analysis was performed using Cox proportional hazards model to determine the prognostic markers for progression-free survival (PFS). Survival curves were obtained through Log-rank test and Kaplan-Meier curve. RESULTS: The median follow-up period was 31 months (24 to 58 months). It was found that SUVmax (≥3.01), SUVmean (≥2.25), MTV (≥25.41 cm³), and TLG (≥55.02) of the primary tumors were significantly associated with PFS in univariate Cox proportional hazards regression. Then regardless of age, gender, co-morbidity, EGFR/ALK mutation status, and treatment program, TLG (≥ 55.02, HR=4.965, 95%CI: 1.360-18.133), TNM stage (Ⅲ/Ⅳ, HR=7.811, 95%CI: 2.977-20.489), pro-gastrin releasing peptide (proGRP) (≥45.65 ng/L, HR=4.070, 95%CI: 1.442-11.487), tissue polypeptide antigen (TPA) (≥68.20 U/L, HR=6.996, 95%CI: 1.458-33.574), alkaline phosphatase (ALP) (≥82.50 IU/L, HR=4.160, 95%CI: 1.416-12.219) and ratio of activated partial thromboplastin time (aPTTR) (≥1.16: HR=4.58, 95%CI: 1.913-10.946) showed the independently relevant to PFS through multivariate Cox proportional hazards analysis. The EGFR mutant (P=0.343) and ALK rearrangement (P=0.608) were not significant either in survival analysis. CONCLUSION High SUV-derived parameters (SUVmax, SUVmean, MTV and TLG) might provide prognostic value to some extent. Especially, TLG, and other clinical features [TNM stage, proGRP, TPA, ALP, and aPTTR] could be independently and significantly associated with PFS of lung adenocarcinoma patients. However, EGFR/ALK gene status could not be effectively relevant to PFS in lung adenocarcinoma patients.
Adenocarcinoma of Lung/genetics* ; Anaplastic Lymphoma Kinase/genetics* ; ErbB Receptors/genetics* ; Fluorodeoxyglucose F18 ; Genes, erbB-1 ; Humans ; Lung Neoplasms/genetics* ; Mutation ; Positron Emission Tomography Computed Tomography ; Prognosis ; Radiopharmaceuticals ; Retrospective Studies ; Tumor Burden

OBJECTIVE: To establish a rapid and accurate "on/off" switch technique consisted of 3'-phosphorothioate-modified allele-specific primers and exo+ polymerase to screen the G719S and T790M mutations of epidermal growth factor receptor (EGFR) gene. The switch was used to identify cervical cancer patients who are sensitive to tyrosine kinase inhibitor (TKI). METHODS: Allele-specific primers targeting recombinant wild-type and mutation-type templates were designed with 3' terminal phosphorothioate modification. Two-directional primer extension was carried out using Pfu polymerase. The G719S and T790M mutations were detected by the technique among cervical cancer tissues. The results were verified by Sanger sequencing. RESULTS: No mutation was detected among the 80 cervical cancer cases, and the results were consistent with that of Sanger sequencing. No significant difference was found between the frequencies of the G719S and T790M mutations between the patient and the control groups (P> 0.05). CONCLUSION A sensitive "on/off" switch technique for detecting the two EGFR mutations was established. The G719S and T790M mutations are not associated with cervical cancer.
Carcinoma, Non-Small-Cell Lung ; Drug Resistance, Neoplasm ; ErbB Receptors ; genetics ; Female ; Genes, erbB-1 ; Humans ; Lung Neoplasms ; Mutation ; Protein Kinase Inhibitors ; Uterine Cervical Neoplasms ; genetics

No abstract available.
Alopecia Areata ; Alopecia ; Epidermal Growth Factor ; Genes, erbB-1

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancers have emerged as key predictive biomarkers in EGFR tyrosine kinase inhibitor (TKI) treatment. However, a few patients with wild-type EGFR also respond to EGFR TKIs. This study investigated the factors predicting successful EGFR TKI treatment in lung adenocarcinoma patients with wild-type EGFR. METHODS: We examined 66 patients diagnosed with lung adenocarcinoma carrying wide-type EGFR who were treated with EGFR TKIs. The EGFR gene copy number was assessed by silver in situ hybridization (SISH). We evaluated the clinical factors and EGFR gene copy numbers that are associated with a favorable clinical response to EGFR TKIs. RESULTS: The objective response rate was 12.1%, while the disease control rate was 40.9%. EGFR SISH analysis was feasible in 23 cases. Twelve patients tested EGFR SISH-positive, and 11 were EGFR SISH-negative, with no significant difference in tumor response and survival between EGFR SISH-positive and -negative patients. The overall median progression-free survival (PFS) and overall survival (OS) of 66 patients were 2.1 months and 9.7 months, respectively. Female sex and Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–1 were independent predictors of PFS. ECOG PS 0–1 and a low tumor burden of extrathoracic metastasis were independent predictors of good OS. CONCLUSION: Factors such as good PS, female sex, and low tumor burden may predict favorable outcomes following EGFR TKI therapy in patients with EGFR wild-type lung adenocarcinoma. However, EGFR gene copy number was not predictive of survival.
Adenocarcinoma* ; Biomarkers ; Disease-Free Survival ; Female ; Genes, erbB-1 ; Humans ; In Situ Hybridization ; Lung Neoplasms ; Lung* ; Neoplasm Metastasis ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor ; Silver ; Tumor Burden

Liquid biopsy for detection of mutation from circulating tumor DNA is a new technology which is attractive in that it is non-invasive. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) is an effective first line drug for advanced non-small cell lung cancer patients who harbor activating EGFR mutation. During the course of treatment, resistance against TKI arises which can be contributed to EGFR T790M mutation in about 50–60% of patients. Third generation TKI may overcome the resistance. In patients who cannot undergo tissue biopsy due to variable reasons, liquid biopsy is an excellent alternative for the detection of EGFR T790M mutation. However, this relatively novel method requires standardization and vigorous quality insurance. Thus, a standard set of guideline recommendations for liquid biopsy for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of provisional guideline recommendations that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.
Biopsy ; Carcinoma, Non-Small-Cell Lung ; DNA ; Genes, erbB-1 ; Humans ; Insurance ; Lung Neoplasms ; Lung ; Methods ; Pathology ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor

PURPOSE: Epidermal growth factor receptor (EGFR) is considered a potential therapeutic target for anti-EGFR therapy in triple-negative breast cancer (TNBC). However, the frequency of EGFR gene mutation in TNBC is low and varies with ethnicity. This study aimed to investigate the incidence of EGFR gene mutation in TNBC. METHODS: EGFR protein expression was evaluated by immunohistochemistry in tissue microarrays of 493 TNBC cases using four different primary antibodies, which included mutation-specific antibodies. For cases with an immunoreactivity level ≥1+, we performed pyrosequencing analysis for EGFR gene mutation. A case was considered mutation-positive when its mutation frequency minus its limit of detection (LOD) was >10%. Cases with mutation frequency higher than LOD were assessed for EGFR gene mutation status using the Cobas assay and by peptide nucleic acid-mediated polymerase chain reaction (PNA-clamping). RESULTS: Among 493 TNBCs, 148 (30.0%) exhibited staining ≥1+ for EGFR, including 78 with 1+, 49 with 2+, and 21 with 3+. Positive EGFR expression (≥2+) was significantly associated with lymphovascular invasion (p=0.010), but not with overall survival (p=0.444) or disease-free survival (p=0.388). None of the 493 TNBCs harbored an EGFR gene mutation. Among 148 cases with an EGFR staining result ≥1+, five (3.4%) showed mutation frequencies (4.4%–10.9%) higher than LOD (2.6%–4.3%) in exons 19 (L747_P753>Q) or 21 (L858R and L861Q) as determined by pyrosequencing. However, Cobas and PNA-clamping failed to detect the presence of EGFR gene mutation in these five cases. CONCLUSION: No activating mutation of EGFR gene of clinical significance was observed in 148 TNBC cases using three commercially available methods. Thus, EGFR gene mutation appears to be an extremely rare event in patients with TNBC.
Antibodies ; Breast Neoplasms ; Disease-Free Survival ; Epidermal Growth Factor* ; Exons ; Genes, erbB-1 ; Humans ; Immunohistochemistry ; Incidence ; Limit of Detection ; Mutation Rate ; Polymerase Chain Reaction ; Receptor, Epidermal Growth Factor* ; Triple Negative Breast Neoplasms*

The increased understanding of the molecular pathology of different malignancies, especially lung cancer, has directed investigational efforts to center on the identification of different molecular targets and on the development of targeted therapies against these targets. A good representative is the epidermal growth factor receptor (EGFR); a major driver of non-small cell lung cancer tumorigenesis. Today, tumor growth inhibition is possible after treating lung tumors expressing somatic mutations of the EGFR gene with tyrosine kinase inhibitors (TKI). This opened the doors to biomarker-directed precision or personalized treatments for lung cancer patients. The success of these targeted anticancer therapies depends in part on being able to identify biomarkers and their patho-molecular make-up in order to select patients that could respond to specific therapeutic agents. While the identification of reliable biomarkers is crucial to predict response to treatment before it begins, it is also essential to be able to monitor treatment early during therapy to avoid the toxicity and morbidity of futile treatment in non-responding patients. In this context, we share our perspective on the role of PET imagingbased phenotyping in the personalized care of lung cancer patients to non-invasively direct and monitor the treatment efficacy of TKIs in clinical practice.
Biomarkers ; Carcinogenesis ; Carcinoma, Non-Small-Cell Lung ; Erlotinib Hydrochloride ; Genes, erbB-1 ; Humans ; Lung ; Lung Neoplasms ; Medical Futility ; Molecular Targeted Therapy ; Pathology, Molecular ; Positron-Emission Tomography ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor ; Treatment Outcome ; Tyrosine

PURPOSE: Recent studies have suggested that specific single-nucleotide polymorphisms (SNPs) contribute to the clinical features of benign prostatic hyperplasia (BPH). In this study, we investigated the relationships of genetic polymorphisms of the epidermal growth factor (EGF) gene and the epidermal growth factor receptor (EGFR) gene with BPH. METHODS: A total of 218 patients with BPH were enrolled in this study. We evaluated the relationship between eight SNPs in the EGF and EGFR genes and prostate volume, prostate-specific antigen (PSA), and International Prostate Symptom Score of BPH patients. Each SNP was genotyped by direct sequencing. Statistical analysis applying codominant, dominant, recessive, and log-additive models was performed via logistic regression. RESULTS: The rs11568943 and rs11569017 SNPs in the EGF gene showed significant associations with prostate volume (rs11568943: P=0.038 in the log-additive model, P=0.024 in the allele distribution; rs11569017, P=0.031 in the dominant model, P=0.028 in the log-additive model, P=0.020 in the allele distribution). Additionally, the rs3756261, rs11568943, and rs11569017 SNPs of the EGF gene and the rs2293347 SNP of the EGFR gene were associated with PSA levels (P<0.05 in each model, respectively). CONCLUSIONS: These results suggest that the EGF gene may affect prostate volume. In addition, the EGF and EGFR genes may be associated with PSA levels in patients with BPH.
Alleles ; Epidermal Growth Factor* ; Genes, erbB-1 ; Humans ; Logistic Models ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Prostate ; Prostate-Specific Antigen ; Prostatic Hyperplasia* ; Receptor, Epidermal Growth Factor*