Study On The Significance Of The Expression And Mutation Of EGFR In Alveolar-epithelial Atypical Hyperplasia

Objective:To investigate the expression and mutation of epidermal growth factor receptor (EGFR) in the alveolar-epithelial atypical hyperplasia (AAH) and its significance, in order to provide a theoretical basis for improving the early diagnosis and treatment of adenocarcinoma in situ (AIS), and for the further meachnism study of the pathogenesis of lung cancer.Methods:The cases of AAH were collected from January2006to June2010in Second Xiang-Ya Hospital of Central South University.41cases were sampling randomly. Immunohistochemistry was applied to detect the protein expression of EGFR and exons19and21of EGFR in AAH tissue. ARMS-PCR was applied to detect mutation of exons19and21of EGFR gene. All the cases and experimental results were analyzed by SPSS.v.12.0and Excel.Results:1. the positive protein expression of EGFR、mutated exons19and21in different grade AAH(1) In41cases, EGFR protein was detected in17high-grade AAH cases, and it also could be detected in17of24low-grade AAH cases (P<0.05).(2) In17high-grade AAH cases, mutation of exon19was detected in13cases. But in24low-grade AAH cases,only lease could detect mutation of exon19(p<0.05).(3) Mutation of exons21was detected in7of17high-grade AAH cases and in2of21low-grade AAH cases(p<0.05).2. The correlation between mutation of exons19、21and the protein expression of EGFRThere’s a positive correlation between mutation of exon19and21of EGFR and its protein expression.3. Correlations of EGFR protein expression, mutation of exons19and21with sex or ages of the AAH patientsEGFR protein expression and mutation of exons19and21were not associated with sex or ages of the AAH patients.4. Comparison between the cases of lung adenocarinoma with concomitant AAH foci and the simple AAH casesIn41cases of AAH, EGFR protein expression and mutation of exons19and21in the cases of lung adenocarinoma with concomitant AAH foci were significant difference with in the simple AAH cases (p<0.05).5. Results of the detection of DNAThe mutation of exons19and21were detected by ARMS-PCR in 11cases. The rate is26.8%(11/41). In these cases,7are mutations of exon19and the other4are mutations of exon21.Compare the11cases of EGFR mutations detected by ARMS-PCR against the16cases of EGFR mutant protein expression detected by Immunohistochemistry, that EGFR protein could be detected in the cases of the mutation of exons19and/or21.There’s a high positive correlation between the two methods.(r=0.75691, p<0.05)Conclusion1. Over-expression of EGFR protein and mutations of exons19and21are closely related to the development of AAH.2. The cases of lung adenocarinoma with concomitant AAH foci has a higher rate of EGFR protein expression and a higher rate of mutation of exon19and21than the simple AAH cases.3. The method of immunohistochemistry has a high positive correlation with the ARMS-PCR, so it can be used to screen AAH with mutation of exons19and21,or not, which can provide a reliable basis for the early diagnosis of lung cancer.