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Summary: Introduction: Mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) are frequently detected in lung adenocarcinomas with bronchioloalveolar (BAC) differentiation and have been associated with increased response to small molecule EGFR inhibitors in some clinical studies. However, further molecular characterization of tumor cells carrying EGFR mutations (EGFR-mut) is warranted. Methods: By DNA sequencing, 120 patients with lung adenocarcinomas (70 tumors with BAC components) were screened for EGFR mutations within exons 18–21. Performing comparative genomic hybridization (CGH) and immunohistochemistry, chromosomal imbalances and protein expression levels of EGFR, ErbB3 and VEGF (vascular endothelial growth factor) were analyzed, respectively. Results: EGFR mutations were detected in 20/120 tumors. Tumors with BAC components carried more frequently EGFR mutations compared to adenocarcinomas without BAC histology (17/70=24% vs 3/50=6.0%; p =0.012). In a subsequent matched-pair analysis, CGH-analysis demonstrated similar mean numbers of chromosomal imbalances for EGFR mutated and wild-type tumors (8.6 vs 7.8 gains; 2.4 vs 2.7 losses), respectively. Furthermore, tumors with mutated EGFR demonstrated gains in chromosomes 7p, 16p and 20q and losses in chromosome 8p. Interestingly, EGFR mutated tumors showed higher VEGF expression (p =0.03) while differences in EGFR expression were not statistically significant. Conclusion: EGFR gene mutations are frequently seen in lung adenocarcinomas with BAC differentiation and can be linked to chromosomal imbalances and increased VEGF expression. [Copyright &y& Elsevier]

Comprehensively investigate the association of CT morphology and clinical findings of adenocarcinoma with EGFR mutation status. Retrospectively included 282 patients who was pathologically proved as lung adenocarcinoma with known EGFR mutation status (mutations: 138 patients, female: 86, median age: 66 years; wildtype: 144 patients, female: 67, median age: 62 years) and their pre-treatment CT scans were analyzed. CT findings and clinical information were collected. Univariate and multivariable logistic regression analysis were performed. Adjusted for age, gender and smoking history of two groups, significantly more patients with pleural tags, pleural and liver metastases were found in the EGFR mutated group (P = 0.007, 0.004, and 0.043, respectively). Multivariable logistic regression analysis found that the model included age, gender, smoking history, air bronchogram, pleural tags, pleural and liver metastasis had a moderate predictive value for EGFR mutation status (AUC = 0.741, P < .0001). Exon-19 deletion was associated with air bronchogram which adjusted for age, gender and smoking history (P = 0.007, OR: 2.91, 95%CI: 1.25–7.79). The evidence of pleural tags, pleural and liver metastases go along with a higher probability of EGFR mutation in adenocarcinoma patients and air bronchogram is positively associated with Exon-19 deletion mutation. [ABSTRACT FROM AUTHOR]