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Objective:To identify the feasibility of pleural effusion detection of epidermal growth factor receptor (EGFR) mutations, echinoderm microtubule-associated protein like 4 (EML4)-anaplastic lymphoma kinase (ALK) and Kirsten rat sarcoma (K-ras) mutation, and to investigate the prognostic and predictive value of EGFR, K-ras and EGFR-ALK in pleural effusion of NSCLC.Methods:We retrospectively analysis 80 NSCLC patients with malignant pleural effusion.EML4-ALK was identified using paraffin embedded tumor cells in pleural effusion by immunohistochemistry (Ventana) and confirmed by fluorescent in situ hybridization.