EGFR mutation of adenocarcinoma in congenital cystic adenomatoid malformation/congenital pulmonary airway malformation: a case report.

An 80-year-old man underwent right upper lobectomy for the resection of multiple cysts accompanied by a nodule. The pathological diagnosis was adenocarcinoma with surrounding atypical epithelial cell proliferation in a Type 1 congenital cystic adenomatoid malformation/congenital pulmonary airway malformation. There was epidermal growth factor receptor mutation in the adenocarcinoma and surrounding atypical epithelial cells that had proliferated. Malignant transformation of congenital cystic adenomatoid malformation/congenital pulmonary airway malformation may be related to the epidermal growth factor receptor pathway in this case, with atypical epithelial cell proliferation as a precursor. We emphasize the importance of complete resection of congenital cystic adenomatoid malformation/congenital pulmonary airway malformation and the possibility of treatment with epidermal growth factor receptor tyrosine kinase inhibitors in epidermal growth factor receptor-mutated cases.

Survival of Patients with Epidermal Growth Factor Receptor-Mutated Metastatic Non-Small Cell Lung Cancer Treated beyond the Second Line in the Tyrosine Kinase Inhibitor Era.

BACKGROUND: The identification of activating mutations in specific genes led to the development of targeted therapies for NSCLC. TKI directed against EGFR-mutations were the first to prove their major efficacy. Medical associations recommend their use as first and second-line metastatic treatments in EGFR-mutated patients. Our objective was to analyze the survival of EGFR-mutated patients treated beyond the second line of treatment. METHODS: We performed a longitudinal, retrospective and analytical study at APHP (Assistance Publique Hopitaux de Paris) Saint Louis, Paris, France, from 1 January 2010 to 31 December 2020 (11 years), on EGFR-mutated patients with metastatic NSCLC which received TKI or chemotherapy (CT) in third-line. RESULTS: Out of about 107 EGFR-mutated patients, 31 patients who benefited from TKI or CT in the third line of treatment were retained for this study. The mean age was 60.03 ± 11.93 years and the sex ratio male/female was 0.24. Mutations of exon 19, 21 and 20 were found in 21 (67.7%), 7 (22.6%) and 7 (22.6%) patients, respectively. Third-line treatment was CT for 16 patients (51.6%) and TKI for the 15 remaining patients (48.4%). Osimertinib was the most used TKI in third-line (n = 10/15; 66.67%). The median duration of third-line treatment was 5.37 months (range 0.53-37.6) and the median follow-up duration was 40.83 months (range 11.33-88.57). There was a significant difference in PFS between patients treated with TKI and CT in third-line (p = 0.028). For patients treated with CT in second-line, there was a significant difference of PFS (p < 0.001) and OS (p = 0.014) in favor of the use of TKI in third-line. CONCLUSIONS: For patients receiving CT in second-line, TKI appears to be a better alternative in third-line compared to CT. Osimertinib may be used in third line treatment if not used before.

Epidermal Growth Factor Receptor (EGFR) Gene Mutation Analysis in Adenocarcinoma of Lung, the First Report from Iran.

BACKGROUND AND OBJECTIVE: Epidermal growth factor receptor (EGFR) gene mutation, especially in exons 18 to 21, is an important predictor of the response rate of lung adenocarcinoma to tyrosine kinase inhibitors. There are variable reports from Asian and European countries, as well as North America, about the frequency of the EGFR mutation in lung adenocarcinoma, yet molecular study about this incidence has been published from Iran. In this study, we investigated the frequency of this mutation in our center, which is the largest referral center in the south of country. This report will be the first published article about EGFR mutational analysis from Iran. METHODS: During the study period (September 2011 till September 2016) i.e. 5 years, there have been 50 cases of pathologically-confirmed lung adenocarcinoma. These cases underwent mutational analysis for exons 18 to 21 of the EGFR gene by PCR and DNA sequencing. All demographic findings were also extracted from the patients' charts and recorded. RESULTS: There were 30 male and 20 female patients, with an average age of 58 years. The overall frequency of EGFR mutation was 28% (14 out of 50). The most common mutation was Del 19 (10 of 14, 71.4%), 3 mutations were found in exon 20 and one mutation was found in exon 21. EGFR mutations were more frequent in women than in men (30% versus 26.7%) and in nonsmokers than in smokers (37.9% versus 14.3%). CONCLUSION: Lung adenocarcinoma with EGFR mutation shows strong association with female non-smokers. Our results showed an intermediate frequency of this mutation, which was higher than results from Western countries and lower than most Asian countries.

Immunohistochemical Evaluation of P53 and Epidermal Growth Factor Receptor Proteins Expression Levels in Gingival Tissue of Opium-dependent Patients.

BACKGROUND: Although evidence indicates that tobacco use is one of the risk factors for oral cancer, the relationship between opium addiction and oral cancer has not yet been evaluated. The present study was performed aiming to evaluate P53 and epidermal growth factor receptor (EGFR) expression in the gingival tissue of opium-dependent patients. METHODS: 102 individuals (70 men and 32 women) were entered in the study. 63 and 39 individuals were included in the opium-dependent group and opium-independent group (control group), respectively. 1 gingival biopsy was taken from each individual. The biopsies were fixed in 10% buffered formaldehyde solution and embedded in paraffin at 56 °C. The slides were then stained with Hematoxylin-Eosin (H & E) and Immunohistochemistry (IHC) evaluation was performed with the antihuman antibodies of P53 and EGFR. The protein expression level was later assessed and data were analyzed statistically. FINDINGS: P53 expression was higher among the opium-dependent group, however the difference was not statistically significant (P = 0.052). EGFR expression was significantly higher among the opium-dependent group compared to the control group (P = 0.006). CONCLUSION: Opium dependency significantly affects EGFR expression in gingival tissue, however it seems to have no significant effect on P53 expression.

EGFR T790M mutation testing within the osimertinib AURA Phase I study.

OBJECTIVES: Reliable epidermal growth factor receptor (EGFR) mutation testing techniques are required to identify eligible patients with EGFR mutation/T790M positive advanced non-small cell lung cancer (NSCLC), for treatment with osimertinib (AZD9291), an oral, potent, irreversible EGFR tyrosine kinase inhibitor (TKI) selective for EGFR-TKI-sensitizing and T790M resistance mutations over wild-type EGFR. There is no current consensus regarding the best method to detect EGFR T790M mutations. The aim of this study was to describe the concordance between local testing, which used a variety of methods, and central testing, using the cobas® EGFR Mutation Test, for EGFR-sensitizing mutations and the T790M resistance mutation. MATERIALS AND METHODS: Tumor samples were obtained from all patients screened for inclusion onto the osimertinib Phase I expansion component of the AURA Phase I/II study (NCT01802632). Samples underwent central laboratory testing for EGFR-sensitizing mutations and T790M resistance mutation using the cobas® EGFR Mutation Test. Results were compared with local laboratory test results, based on other testing methodologies including Sanger sequencing, therascreen®, PNAClamp™, and Sequenom MassARRAY®. RESULTS: Central laboratory testing was successful in 99% of samples passing histopathology review and testing success rates were comparable across the three central laboratories. Concordance between central and local testing for common sensitizing mutations was high (>98%) and concordance for the T790M mutation was also high (>90%). Tumor heterogeneity, along with other technical factors may have influenced this result. CONCLUSIONS: Within the osimertinib AURA Phase I study, EGFR mutation testing across three centralized laboratories using the cobas® EGFR Mutation Test was feasible and successful, with strong concordance between local and central laboratory results, including for T790M. The cobas® EGFR Mutation Test has subsequently been approved as the companion diagnostic test for osimertinib in the USA and Japan.

Successful treatment with afatinib after grade 3 hepatotoxicity induced by both gefitinib and erlotinib in EGFR mutation-positive non-small cell lung cancer.

Hepatotoxicity is a major cause of the withdrawal of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) when treating EGFR mutation-positive non-small cell lung cancer (NSCLC). We report a case in which gefitinib- and elrotinib-induced severe hepatotoxicity arose in a patient with the uridine diphosphate glucuronosyltransferase isoform 1A1 (UGT1A1) and cytochrome p450 3A5 (CYP3A5) poor metabolizer phenotypes. Afatinib is not significantly metabolized by cytochrome p450-mediated pathways. We describe successful management of the patient's tumor by switching to afatinib. Evaluation of single nucleotide polymorphisms (SNPs) in metabolic enzymes might be useful to predict severe hepatotoxicity induced by EGFR-TKIs.