Expression of ERCC1 and its clinicopathological correlations in non-small cell lung cancer

Abstract

Excision Repair Cross-Complementing Group 1 (ERCC1) is an important DNA repair gene, playing critical role in nucleotide excision repair pathway and having a significant influence on genomic instability. Some studies support that ERCC1 might be a potential predictive and prognostic marker in non-small cell lung cancer (NSCLC). ERCC1 has also been shown to be a promising biomarker in NSCLC treated with a cisplatin-based regimen. Therefore, the determination of ERCC1 expression at DNA, mRNA and protein level in different stages of NSCLC is still an important topic in the cancer. Ninety-one formalin-fixed paraffin-embedded tumor samples histopathologically diagnosed as NSCLC were examined in this study. ERCC1 expression at protein level were scored by immunohistochemistry. The gene amplification and mRNA expression levels for ERCC1 were determined by real-time quantitative PCR. There was complete concordance among the three methods in 39 tumor samples (42.9%). A strong correlation was found between DNA amplification and mRNA expression (r=0.662) while there was no correlation between mRNA and protein assessment for ERCC1 expression (r=-0.013). ERCC1 expression at mRNA and DNA level (63.1 and 84.2%, respectively) in tumors at stage III was higher than at the other stages. In contrast, the protein expression at stage II and III (56.6 and 52.6%, respectively) of NSCLC was lower than that of tumors with stage I NSCLC. These results show that the mechanism by which ERCC1 expression might play a role in tumor behavior. This study was also confirmed that the appropriate validation and qualification in methods used for ERCC1 status were needed before its clinical application and implementation.

Excision repair cross complementation group 1 is a chemotherapy-tolerating gene in cisplatin-based treatment for non-small cell lung cancer

“…Previous (30,31) including our studies (28) indicated that mRNA and protein expression of ERCC1 in NSCLC tumors was higher than that in adjacent normal tissues, so it was reported that ERCC1 may be associated with the development of NSCLC. As further confirmation, in the present study, ERCC1 gene was cloned and transfected into the NSCLC H1299 cells with no intrinsic ERCC1 expression.…”

“…Correspondingly, the expression of the associated proteins, P-glycoprotein (P-gp) and multidrug resistanceassociated protein (MRP), had no significant difference as well between the two cell lines (C). variations with platinum-based chemotherapy response and resistance (30)(31)(32)(33). Although an exact conclusion has not been made due to the differences of these studies in trial design and laboratory tests (24,34), ERCC1 has attracted great attention of the NSCLC investigators.…”

Commercial Laboratory Testing of Excision Repair Cross-Complementation Group 1 Expression in Non-Small Cell Lung Cancer

“…Second, low expression of ERCC1 has been shown to be associated with other genomic alterations, including those that affect sensitivity to nonplatinum chemotherapies [33,34]. Third, others have previously noted that thresholds for ERCC1 "expression" had been arbitrarily assigned and inadequately validated [35]. Fourth, several prior studies had been unable to confirm the predictive utility of ERCC1 expression in platinumtreated lung cancer patients [31,36].…”

Inhibitory Role of the Small Leucine-Rich Proteoglycan Biglycan in Bladder Cancer

“…For small, unifocal, superficial, low-grade bladder cancers, the estimated 5-year risk of progression to a muscle-invasive tumor is only 0.8%. Recently, several genes have been identified that are associated with bladder cancer progression and poor prognosis, such as excision repair cross-complementing group 1 (ERCC1), matrix metalloproteinase-7 (MMP-7), hyaluronidase 1 (Hyal-1) [33-35]. The latter genes point to an important role of the ECM microenvironment in bladder cancer progression.…”