Molecular Prognosis And Predictions Of Response To Adjuvant Chemotherapy In Stage Ⅰ-Ⅲ Resected Patients With Non-Small Cell Lung Cancer

【Objective】To summarized clinical characters and features of treatments and survival in stageⅠ-Ⅲresected NSCLC patients,to explore subtential molecular predictors of therapeutic effect and recurrence risk,to discuss effect of target therapy on recurrence patients and to look for clinical and molecular predictors of TKI efficiency,to provide evidences for establishing individual postoperative adjuvant chemotherapy model and carrying out prospective clinical trials based molecular type in NSCLC patients.【Methods】The cases who received surgery therapy in our hospital from Jan. 2000 to Dec.2007 and were diagnosed with stageⅠ-ⅢNSCLC were analyzed.Those who were lost of follow up or can't finish at least one cycle adjuvant chemotherapy were deleted.And immunohistochemistry(IHC) results of routine seven biomarkers of all cases were reviewed.Paraffin-embedded samples of all cases were collected to detect expression of ERCC1,RRM1,βtubulinⅢ,pERK1/2 and pAKT1 by IHC method.Those who received with TKI and can be evalued of effect after recurrence were picked up to further detect EGFR and Kras mutation from Paraffin-embedded samples;survival rate and disease free survival(DFS) were analyzed by SPSS 16.0 software.【Results】163 cases were collected.The median follow up was 37 months. Untill the destinaion of study,there were only 47 cases dead,the median overall survival(OS) was not available.Three-year OS was 68.2%;and the median DFS was 24.4 months.Early symtoms,adenocarcinoma,N2 stage and less than 4 cycles chemotherapy predicted poor prognosis.The DFS in over-expression of TopⅡαgroup was significant longer than weak-expression group(not available vs 19.4 months,p=0.006).And in weak-expression group,the regimen with NVB had prolonged DFS(48.2 month vs15.7 months,p=0.043) compared with any other regimens.In less than 4 cycles chemotherapy strata,the DFS in positive group of ERCC1 was longer than negtive group(33.0 vs 9.6 months,p=0.046),on the contrary,the DFS in positive group of ERCC1 was shorter than negtive group in another chemotherapy cycle strata(18.6 months vs not available,p=0.029).The DFS in groups with weakexpression pAKT1 and with overexpression pERK1/2 was respectively longer than overexpression pAKT1 and negtive pERK1/2(34.2 vs 15.6 months,p=0.020 and not available vs 19.4 months,p=0.01).Both of them showed no selective in chemotherapy regimens.9 cases of EGFR mutation and 5 cases of Kras mutation was observed in 35 recurrence cases.And all patients with EGFR mutation have benefited from TKI,while 5 cases of Kras mutation were no response to TKI.Besides EGFR mutation,smoke and overexpression of pAKT1 were poor independent prognosis factors of efficiency of TKI.In COX proportional regression analysis of 35 recurrence cases,only smoke statue could impact overall survival.【Conclusion】Routine 4 cycles adjuvant chemotherapy was approved to contribute to DFS for common patients.TopⅡα,βtubulinⅢ,pAKT1 and pERK1/2 were all independent prognosis factors of DFS,which may be used to select special patients who can benefit from adjuvant chemotherapy.All mutation of EGFR 19 and 21 exons have predict to benefit from TKI,while Kras mutation were the sign of no response to TKI.Besides EGFR mutation,smoke statu and expression of pAKT1 can be employed to predict TKI efficiency.