The Relationship Between EGFR Gene Mutation And ERCC1Gene In Lung Adenocarcinoma Receiving Platinum-based Neoadjuvant Chemotherapy

Background：With the development of the random ized controlled trial, a goodprospect has been showed in Neoadjuvant Chemotherapy. It has been a significant part inthe multi disciplinary comprehensive treatment. It has been known that NeoadjuvantChemotherapy can decrease the tumor load, improve resection rate, prolong the survivaltime. But there are so many disputes such as toxic reaction, complications after surgery,survival time and so on. At present, EGFR-TKI has been used widely by the lung cancerpatients. The good therapeutic effect is always related with the EGFR gene mutation.ERCC1expresion in lung cancer tissue is an important factor that it can forcast the resultof the platinum-based adjuvant Chemotherapy and will be an important index inindividualized treatment in lung cancer. In our study, we will assess the clinical efficacy ofplatinum-based neoadjuvant chemotherapy and to analyze if the platinum-basedneoadjuvant chemotherapy is related to the change in states of EGFR genetic mutation andRCC1expression.PartⅠ Neoadjuvant Chemotherapy in Lung Adenocarcinoma withClinical IIa-IIIa StageObjective：To analyze the clinical efficacy of neoadjuvant chemotherapy in lungadenocarcinoma with IIa-IIIa stage.Methods:107patients are treated in hospital and diagnosed lung adenocarcinoma.The preoperational sample is obtained with fiberoptic bronchoscopy, lung puncture, videomediastinoscopy or thoracoscope. The specimens will be gained again by radical resectionof lung cancer after the Platinum Doublet Neoadjuvant Chemotherapy, i.e. Pemetrexed(500mg/m2,d1) and Cisplatin (75mg/m2,d1) for two courses of treatment. According theRECIST standard, we assessed the toxic reaction and clinical efficacy. Results: According to RECIST standard, the percentage of partial response (PR)following the neoadjuvant chemotherapy is27.1%（29/107）, stable disease (SD) is61.7%（66/107） and progressive disease (PD) is11.2%(12/107). There is no significantdifference in immunity function and complicatopngs between group I and group II aftersurgery. Meanwhile, there is a significant difference between the DFS in neoadjuvantchemotherapy group and surgery group with IIIa stage.(p=0.0388).Conclusion: Neoadjuvant chemotherapy can prolong the survival time in cIIIa lungadneocarcinoma, and can not increase the complication rates and influence the immunityfunction after surgery.PartII EGFR Gene Mutation Status Shift in Lung Adenocarcinomapre and post Neoadjuvant ChemotherapyObjective: To analyze the relationship between EGFR mutation status shift andneoadjuvant chemotherapyMethods: The state of EGFR genetic mutation in the specimen of tumor tissue beforeand after the chemotherapy is tested with direct sequencing, including deletion of exon19and point mutation of exon21, and used to compare with the characteristics of clinicalpathology. The Kaplan-Meier is conducted for the survival analysis of the difference ofdisease-free survival (DFS) between the patients with mutant and wild-type EGFRsfollowing the chemotherapy, for the establishment of the COX survival analysis model andthe analysis for the relevant elements affecting prognosis.Results: The rate of EGFR genetic mutation in tumor tissue before and after thechemotherapy is57.0%(61/107) and65.4%(70/107) respectively, showing no statisticaldifference (P=0.067). EGFR genetic mutation is identified more in females(pre-chemotherapy: P=0.003; post-Chemotherapy: P=0.012) and non-smokers(pre-chemotherapy: P=0.007; post-chemotherapy: P=0.000) without any relation withother pathological elements (P>0.05). Before or after the chemotherapy, DFS in thepatients with mutant or wild EGFR in the preoperative and postoperative follow-up showsbetter level in the mutant patients than that in wild ones with the significant statisticaldifference observed between the both (P=0.039)（P=0.0135）. COX risk model shows thelymph node metastasis in mediastinum (P=0.000), degree of differentiation (P=0.000), size of tumor (P=0.001) and the change in state of EGFR genetic mutation (P=0.044) may berelated to prognosis.Conclusion: The platinum-based neoadjuvant chemotherapy cannot change the stateof EGFR genetic mutation in the tissue of lung adenocarcinoma.PartIII The Relationship between ERCC1Expression and EGFR GeneMutation Status Shift After Platinum-based NeoadjuvantChemotherapyObjective: To analyze the relationship among ERCC1expression, EGFR genemutation status shift and neoadjuvant chemotherapy in lung adenocarcinoma.Methods: ERCC1expression in lung adenocarcinoma tissue with different status ofEGFR genetic mutation following the neoadjuvant chemotherapy is analyzed withimmunohistochemistry and compared with the efficacy of neoadjuvant chemotherapy.Results: The result of immunohistochemistry: there is a significant differencebetween the ERCC1expression and the efficacy of neoadjuvant chemotherapy(P=0.000).The rate of ERCC1negative expression in group of change in state EGFR genetic mutationis (73.7%,14/19) higher slightly than that in group of non-change one (71.6%,63/88), withthe significant statistical difference observed (P=0.021).Conclusion: There is significant correlation between the ERCC1expression and theefficacy of platinum-based chemotherapy. The positive expression of ERCC1may relate tothe constant state of EGFR genetic mutation in the tissue of lung adenocarcinoma.