EGFR Mutations in Lung Adenocarcinoma: Prevalence, Histopathological Correlations, and Prognostic Implications : A Systematic Review

Abstrak

Background: Mutations within the epidermal growth factor receptor (EGFR) play a vital role in both the development and treatment of lung adenocarcinoma. While these mutations can offer insights into the efficacy of targeted therapies, the relationships between EGFR mutations, the microscopic appearance of the cancer (histopathological features), and the progression of the disease across its different stages remain somewhat unclear. This systematic review was undertaken to investigate the prevalence of EGFR mutations, their correlation with histopathological characteristics, and their impact on the prognosis of patients diagnosed with lung adenocarcinoma. Methods: A comprehensive search of PubMed, Scopus, and Embase databases was conducted, adhering to the PRISMA guidelines. The studies incorporated were either observational or interventional studies that documented EGFR mutation status in lung adenocarcinoma confirmed through histopathology, providing data on prevalence, histopathological features, or survival outcomes. Data extraction and qualitative synthesis were carried out across predefined outcome domains. Results: The review encompassed six studies, involving over 3,900 patients. The prevalence of EGFR mutations ranged from 38.0% to 72.5%, with higher rates consistently observed within Asian populations. Exon 19 deletions and exon 21 L858R substitutions represented the most common EGFR mutations across the studies. Microscopically, EGFR-mutant tumors frequently exhibited lepidic and acinar growth patterns, moderate differentiation, and lower histologic grade. In advanced-stage lung adenocarcinoma, EGFR mutations—particularly exon 19 deletions—were associated with improved overall survival, primarily due to the effectiveness of EGFR tyrosine kinase inhibitors. Conversely, in early-stage resected disease, EGFR mutation status did not independently predict prognosis; histologic grade and pathological stage were more significant factors. Histologic transformation to small-cell lung carcinoma was a notable mechanism of disease progression linked to poor outcomes. Conclusions: EGFR mutations are frequently detected in lung adenocarcinoma and exhibit specific associations with histopathological features and stage-dependent prognostic impacts. Although EGFR mutations improve survival in advanced disease owing to targeted therapy, their independent prognostic value in early-stage disease is limited. A combined molecular and histopathological approach is crucial for accurate prognosis and personalized management of lung adenocarcinoma.