| Backgroud Platinum-based regiments are the cornerstones in chemotherapy of early stage non-small cell lung cancer after resection.However,the survival benefits associated with platinum-based chemotherapy is marginal.It is essential to select patients who can benefit from this management.ERCC1 is a key enzyme in the repair of platinum-DNA adducts and ERCC1 overexpression is associated with resistance to platinum.RRM1 is one of key enzymes in DNA synthesis and repair,and its overexpression has been linked to the tumor's resistance to platinum drugs and gemcitabine.ClassⅢβ-tubulin is reported to be correlated with resistance to tubulin-binding agents.Objectives By investigating the expression of ERCC1,RRM1,classⅢβ-tubulin in resected patients with non-small cell lung cancer and exploring the influnence on adjvant chemotherapy and prognosis in NSCLC,we expect that the selection of patients according to key genetic characteristics can help to tailor chemotherapy.Methods From June 1994 to Agust 2007,105 patients with resected NSCLC obtained follow-up.Immunohistochemistry was used to evaluate ERCC1,RRM1,classⅢβ-tubulin expression in resected lung tumor samples.The relationship between clinic pathological parameters,adjvant chemotherapy and survival, expression of these three proteins and clinic pathological parameters were analyzed.Then we carried on subunit analysis,and all patients were divided three groups:subgroup of patients with surgery alone(n=42),with receiving platinum-based regiments in adjuvant management(n=63),with receiving platinum/gemcitabine chemothrapy(n=29).Overall survival were compared in relationship to expression of each ofproteinss in every subunit.Results 1.Pathological types(P=0.001),TNM staging(P=0.000),lymph node involvement(P=0.000) and resection natures(P=0.000) are prognostic factors for NSCLC following the surgical procedure.2.The patients with resected stageⅡ～Ⅳnon-small cell lung cancer had longer median survival if include adjvant chemotherapy(29 months vs 9.5 months,P=0.015).3.Positive rate of immunostaining for ERCC1,RRM1,classⅢβ-tubulin was 43.8%,83.5%,83.5%,respectively.4.There was a strong correlating between RRM1 and classⅢβ-tubulin expression(r_s=0.298,P＜0.002).No significant correlation between ERCC1 and RRM1 was found.5.Concomitant expression of ERCC1,RRM1,classⅢβ-tubulin reveals that the patients who express ERCC 1(-),RRM 1(+),ClassⅢβtubulin(+) or ERCC1(+),RRM1(+),ClassⅢβtubulin(+) accout for 39.05%,36.19%,respectively,which is the leading proportion of NSCLC gene expression.6.Subgroup analysis of NSCLC patients treated with platinum-based adjvant chemotherapy after resection:On univariate analysis,median overall survival was 23months for ERCC1-positive and 68.5 months for ERCC1 -negative(P=0.000).Median overall survival in patients with RRM1-negative was significantly longer than RRM1-positive(84months vs 33.7months,P=0.048).Concomitant negative expression of ERCC1 and RRM1(n=6)were predictive of a better outcome(P=0.004).7.At multivariate analysis,ERCC1 was independent predictive factor of survival for NSCLC patients treated with platinum-based adjvant chemotherapy after resection.8. Subgroup analysis of NSCLC patients treated with platinum/gemcitabine adjvant chemotherapy after resection:Median survival time in patients with ERCC1-negative was significantly longer(36months vs 28.5months,P=0.014) as well as in patients with RRMl-negative(84months vs 30months, P=0.020).Concomitant negative expression of ERCC1 and RRM1 were predictive of a better outcome(84months vs 28.5months,P=-0.009).No correlation between classⅢβ-tubulin expression and survival was found(P=0.464).9.At multivariate analysis,TNM stage,lymph node involvement,ERCC1 were independent predictive factors of survival for NSCLC patients treated with platinum/gemcitabine adjvant chemotherapy after resection.10.Subgroup analysis of resected patients with NSCLC:Patients with a positive ERCC1 expression survived longer than ERCC1-negative patients(25.5months vs 13 months, P=0.037),Conversly,patients negative for classⅢβ-tubulin had a significantly longer median overall survival than those positive for classⅢβ-tubulin(73 months vs 15 months,P=0.038).11.At multivariate analysis,TNM staging,lymph node involvement,ERCC1 were independent prognosis factors of survival for resected patients with NSCLC.Conclusion 1.Concomitant expression of ERCC1,RRM1,classⅢβ-tubulin reveals that the patients who express ERCC 1(-),RRM 1(+),ClassⅢβtubulin(+) or ERCC1(+),RRMI(+),ClassⅢβtubulin(+) accout for 39.05%,36.19%,respectively,which is the leading proportion of NSCLC gene expression.2.ERCC1 expression was identified as not only a positive prognostic marker in resected NSCLC patients but also a predictive marker of the survival with NSCLC patients treated with platinum-based adjvant chemotherapy after resection.3.ERCC1 and RRM1 are molecular marks for resistance to platinum for NSCLC patients treated with platinum-based adjvant chemotherapy after resection, Patients with negative ERCC1 and/or RRM1 expression survived longer than positive expression petients.4.Patients with negative ERCC1 and/or RRM1 expression associciated with good survival in NSCLC patients treated with platinum/gemcitabine adjvant chemotherapy after resection.5.In resected NSCLC patients,a positive ERCC1 expression or negative-classⅢβ-tubulin expression is predictive of survival.
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