Clinical Significance Of Expression Of ERCC1, Class Ⅲ β Tubulin In Resected Patients With Non-small Cell Lung Cancer & Association Between Polymorphisms Of ERCC1 And Response And Survival In Advanced Non-small Cell Lung Cancer Patients Treated With Cis

Background and objective: Recent basic and clinical studies have showed that ERCC1 and Class IIIβTubulin were predictors of survival in resected patients with non-small cell lung cancer and associated with drug-resistance of cisplatin, vinorelbine and paclitaxel, polymorphisms of ERCC1 associated with response and survival in advanced non-small cell lung cancer treated with platinum-based chemotherapy. In our study, expression of ERCC1 and Class IIIβTubulin will be detected to analyze whether they would be predictors of prognosis of resected patients with non-small cell lung cancer in stage I-IIIB disease. Allele frequency of ERCC1 C8092A and T19007C will be tested to investigate the association between polymorphisms of ERCC1 C8092A and T19007C and response and survival in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy.Methods:The expression of ERCC1 and Class IIIβTubulin were detected by immunohistochemical assay in one hundred and sixty resected lung cancer primary tumors, fifty matched cancer and adjacent normal tissues, and forty benign tissues. Gene polymorphisms of ERCC1 C8092A and T19007C in sixty-eight patients with advanced non-small cell lung cancer treated with platinum-based chemotherapy were examined by polymorphisms chain reaction and sequencing.Results:The expression rates of ERCC1 and Class IIIβtubulin in non-small cell lung cancer is 46.9%, 49.4% respectively, both are correlated to gender, high expression of them can be found in male patients. Positive expression of ERCC1 is associated with longer survival for patients with postoperative adjuvant chemotherapy in stage I, but with shorter survival for patients with postoperative adjuvant chemotherapy in stage II-IIIB. The expression of Class IIIβtubulin is unrelated to overall survival in stage I-II disease, while negative expression of Class IIIβtubulin is associated with longer survival in stage III disease. For NSCLC patients with post-operative adjuvant chemotherapy, negative expression of ERCC1 and Class IIIβtubulin is associated with longer survival. There are three genotypes of ERCC1 C8092A, which gene frequencies of C/C,C/A,A/A are 38.2%, 52.9%, and 8.8%, respectively ; There are three genotypes of ERCC1 T19007C, which gene frequencies of C/C, C/T, and T/T are 57.4%, 36.8%, and 5.9%, respectively.Compared with patients carrying genotype C/A and A/A, there is no significant difference in response and progress free survival in patients carrying genotype C/C in ERCC1 C8092A. Compared with patients carrying C/A and A/A, there is also no significant difference in response and progress free survival in patients receiving platinum-based chemotherapy carrying C/C in ERCC1 C8092A. Conclusions: Positive expression of ERCC1 is a good independent factor of prognosis in stage I disease, but for patients in stage II-IIIB negative expression of ERCC1 is associated with better advantage from postoperative adjuvant chemotherapy. The expression of Class IIIβtubulin is unrelated to overall survival in stage I-II disease. Negative expression of Class IIIβtubulin is an independent factor of longer survival for NSCLC patients with post-operative adjuvant chemotherapy in stage III disease. Negative expression of ERCC1 and Class IIIβtubulin is associated with longer survival for NSCLC patients with post-operative adjuvant chemotherapy.Gene polymorphisms of ERCC1 C8092A and T19007C have nothing with response and prognosis free survival in patents with advanced non-small cell lung cancer receiving platinum-based chemotherapy.