Clinical Significance Of EGFR Gene Mutations And Expression Of Downstream Phosphorylated Signal Transduction Proteins AKT And ERK Protein Expression In Non-Small Cell Lung Carcinoma

Objective To detect the the mutations of epidermal growth factor receptor (EGFR) gene and the expression of its downstream signal transduction proteins AKT and ERK phosphorylated and investigate the relation with clinc-pathology charaters and prognostic effect in NSCLC. To explore a more reliable assay for selecting the patients who need the therapy to specific molecular target.Methods 103 cases of NSCLC surgery specimens were collected in xiangya hospital from September 2003 to July 2010. None of these patients was treated by chemotherapy or radiotherapy before surgery.Their detail information about survival situation was collected by telephone and mail investigation. Clinical information of these patients including age, pathological type, smoking status, TNM stage, and lymph node metastasis was got by searching the medical records.EGFR mutation in exons 19 and 21 was detected by using PCR and direct sequencing method. p-AKT,p-ERK were detected by using immunohistochemistry. Stafistical analysis was performed using SPSS statistical software package (17.0). P values≤0.05 indicated statistically significant difference.Results (1) The positive rate of EGFR mutation of exon 19 and 21 in NSCLC was 33.0%(34/103), including 24 cases (70.6%) of in-frame deletions at exon 19, and 10 cases substation at L858R sites at exon 21 was observed in this group of NSCLC. The express positive rate of EGFR gene mutation was different in smoking and pathological characteristics whereas no different were seen considering sex, age, T stage, N stage, M stage, total stage. The positive rate of EGFR mutation was different in adenocarcinoma, squamous cell carcinoma and bronchi oal velar carcinoma (22.6%vs 47.1%vs 57.1%). (2) For the 103 NSCLC patient specimens, the positive rate of p-AKT was 56.3% (58/103). The expression rate of p-AKT was higher in EGFR mutation group positive than negative group (76.9%versus 46.4%); The express positive rate of p-AKT was different in smoking and pathological characteristics whereas no different were seen considering sex, age, T stage, N stage, M stage, total stage.(3) The positive rate of p-ERK was 30.1%(31/103). The express positive rate of p-ERK was different in age, N stage, M stage and pathological characteristics whereas no different were seen considering sex, smoking, T stage, total stage. (4) The overall survival between the positive and the negative of EGFR mutation and p-AKT and p-ERK was different, but with no significant difference (Log Rank,P>0.05).Conclusion (1) EGFR gene mutation and EGFR downstream signal molecular including p-AKT and p-ERK are high express in NSCLC. (2) Both of EGFR gene mutation and p-AKT protein expressions have relationship with smoking status and pathological type. The express rate of EGFR mutation in non-smoking people was higher than smoking. (3) Overexpress of p-ERK may correlate with degree of differentiation, invasion and metastases in the NSCLC. On univariate analysis, we have not find p-ERK expression correlated with poorer OS. (4) For NSCLC with the expression positive and negative of EGFR gene mutation and p-AKT have no differentice about the overall survives. The expression of EGFR gene mutation and p-AKT were positively correlated with each other. EGFR gene mutation may cause more activation of related PI3K-PKC-IKK signal transduction pathways.