Comparison Of EGFR Mutation Statuses In Paired Tissue And Plasma Samples In Non-small Cell Lung Cancer Patients

ObjectivesEpidermal growth factor receptor (EGFR) mutations play essential roles in the treatment of non-small cell lung cancer (NSCLC) patients using EGFR tyrosine kinase inhibitors (EGFR-TKIs). EGFR mutations could predict the efficacy of EGFR-TKIs. To detect EGFR mutations in blood cell-free DNA seems promising. However, the mutation statuses in the plasma/serum were not always consistent with those in the tissues. The aims of this study were to compare the mutation statuses in the plasma compared to those in tissues, and thus to determine the specific subgroups of non-small cell lung cancer patients who may be the best candidates for EGFR mutation analyses using blood cell-free DNA.MethodsA total of111pairs of tissue and plasma samples before radio-and chemo-treatment were collected. Of the111patients,51were stage I-IIIA,60were stage IIIB-IV;35were squamous cell carcinoma,76were non-squamous cell carcinoma. Mutant-enriched PCR and sequencing analyses were performed to detect EGFR exon19deletions and L858R mutation in exon21. Clinical characteristics including gender, age, smoking history, disease stage, histopathology, and tumor differentiation were collected. Patients were subgrouped according to clinical characteristics. McNemar test was performed to compare EGFR mutation statuses by tissue and plasma samples, and Kappa test was determined to quantify the agreement of both methods. EGFR mutation statuses in tissue were considered as golden standard. Consistency, sensitivity and specificity were analyzed in subgroups by chi-square and Fisher’s exact tests.ResultsMutations were found in43.2%(48/111) of the patients in tissue or plasma samples. Of the111patients,45(40.5%) were detected with EGFR mutations in tissue samples and19(17.1%) in plasma samples. EGFR mutation rates were significantly higher in subgroups of female (57.1%vs32.9%, P=0.0156), never-smoker (51.9%vs29.8%, P=0.0182) and non-squamous cell carcinoma (56.6%vs5.7%, P<0.0001).The overall consistency of the EGFR mutation statuses of the111paired plasma and tissue samples was71.2%(79/111). The sensitivity and specificity rates of detecting EGFR mutations in the plasma were35.6%(16/45) and95.5%(63/66), respectively. Subgroup analyses show that the consistency in poor differentiation group was91.4%, which was significantly different from other subgroups according to tumor differentiation (P=0.0014). The disease stage and tumor differentiation subgroups showed significantly different detection sensitivities; the sensitivity was10%in early-stage patients and56%in late-stage patients (P=0.0014). For patients with poorly differentiated tumors, the sensitivity was77.8%, which was significantly different from those with highly differentiated (20%, P=0.0230) and moderately differentiated (19%,P=0.0042) tumors.ConclusionsTissue sample is the best material for EGFR gene mutation test. Plasma could be an alternative when tissue sample is insufficient. Blood analyses for the EGFR mutations may be effectively used in late-stage patients or patients with poorly differentiated lung cancer.