Although there is a similar trend for RRM1 protein expression, this was not statistically significant. ERCC1 and RRM1 and in older patients and those with adenocarcinoma for RRM1. Low ERCC1 scores indicated significant benefit from adjuvant chemotherapy [hazard ratio (HR) = 0.73 for chemotherapy versus control,P= 0.02]. Although all other survival associations were not statistically significant, low RRM1 scores trended to indicate benefit from adjuvant chemotherapy (HR = 0.84,P= 0.25), and ERCC1 scores were marginally prognostic of survival (HR = 0.77 for high versus low scores,P= 0.10). We conclude that contributing center and specimen quality substantially affect the levels of both markers. Future trials should incorporate the collection and processing of tumor specimens prospectively on standardized protocols to better reveal the impact of biomarkers on clinically relevant outcomes. Tumor progression and resistance to therapeutic interventions are major obstacles to improving the outcome for patients with nonsmall cell lung cancer (NSCLC). Although notable progress has been made in the treatment of NSCLC, it is still associated with a poor prognosis for most patients. Modern techniques have facilitated the identification of genes and their products that may play a role in disease progression and patient GW9508 response to therapy. Among these are the excision repair cross completing group 1 gene product (ERCC1) and the regulatory subunit of ribonucleotide reductase (RRM1). ERCC1 is usually a component of the 5 endonuclease of the nucleotide excision repair complex, and it is crucial for the repair of DNA damage caused by interstrand and intrastrand cross-links that prevent both replication GW9508 and transcription.1Previous work in patient-derived specimens has shown that elevated levels of ERCC1 are associated with improved outcomes in patients treated with surgical resection alone.2,3It is presumed that this improvement in survival is a result of increased DNA damage repair capacity, and evidence of a reduced lung cancer risk in individuals with increased levels for GW9508 nucleotide excision repair genes exists.4,5However, in patients who require cytotoxic chemotherapy, in particular with brokers that induce DNA adducts and cross-links, high levels of ERCC1 are associated with reduced efficacy presumably through the increased efficiency of repair of platinum-induced DNA damage.1,3,6 RRM1 functions as the regulatory subunit of ribonucleotide reductase and controls substrate specificity and the on/off function of ribonucleotide reductase, whereas the catalytic subunit (RRM2) converts nucleoside diphosphates to ITGA7 the corresponding deoxynucleotides.7Results from multiple independent laboratories and clinical studies have shown that RRM1 is the dominant determinant of efficacy for the chemotherapeutic agent gemcitabine, a nucleoside analog.6,813In addition, RRM1 suppresses carcinogen-induced lung tumorigenesis in experimental animal models, which appears to be a result of increased DNA damage repair capacity in the presence of elevated RRM1.14It also suppresses tumor progression as shown by decreased cellular migration and invasionin vitroand suppression of metastasis formation in mouse models, resulting in increased animal survival.15,16In patients with NSCLC and pancreatic cancer who had a complete surgical resection and no adjuvant therapy, survival was longer for those with high levels of expression compared with those with low levels of expression.1719 Although little controversy exists regarding the association between ERCC1 and RRM1 with platinum and gemcitabine efficacy, there are recent reports of ERCC1 and RRM1 either not being significantly associated or potentially being inversely associated with the survival of NSCLC patients after a complete surgical GW9508 resection.20,21Knowing the prognostic impact of both genes around the survival of patients not undergoing chemotherapy with a platinum agent and/or gemcitabine is usually important for the design and interpretation of clinical trials that incorporate both genes into a treatment decision algorithm, in particular if this GW9508 treatment is usually given in a curative attempt in completely resected patients. Two clinical studies in patients with advanced NSCLC.