ERCC1 mRNA expression is not associated with response and survival after platinum-based chemotherapy regimens in advanced non-small cell lung cancer.
BACKGROUND
Platinum-based therapy is pivotal to the treatment of advanced non-small cell lung Cancer (NSCLC). Excision repair cross-complementation group 1 (ERCC1) is a key component of the platinum-DNA repair machinery responsible for nucleotide excision repair. We sought to determine the influence of ERCC1 mRNA expression in advanced NSCLC on chemotherapy response, toxicity, and survival after platinum-based chemotherapy.


METHODS
Patients randomized to a phase III trial of platinum-based chemotherapy were eligible for inclusion. Formalin-fixed paraffin-embedded tumor biopsies were retrieved for mRNA extraction and purification before quantitative real-time polymerase chain reaction analysis using Taqman technology. Expression data were correlated with treatment response, toxicity, and overall survival.


RESULTS
Sixty-six patients were enrolled. No statistically significant relationship existed between ERCC1 mRNA expression and response to chemotherapy (p = 0.794) or hematological toxicity. No statistically significant difference in median survival was demonstrated according to ERCC1 expression (high expression, 415 days, 95% confidence interval [95%CI]: 197-633 days; low expression, 327 days [95%CI: 211-433 days]; p = 0.801). High ERCC1 mRNA expression was associated with a hazard ratio for death of 0.96 (95% CI 0.919-1.004; p = 0.08).


CONCLUSIONS
In contrast to recent publications, ERCC1 mRNA expression in our study did not favor a prognostically better outcome after platinum-based chemotherapy in advanced NSCLC. We explore potential reasons for this, including the need for cautious interpretation of mRNA expression data from archival materials and highlight the need for additional translational research linking gene expression with a promising ERCC1 polymorphism.
Booton
Richard
R
Christie Hospital NHS Trust & Paterson Institute for Cancer Research, Manchester, United Kingdom. r.booton@btopenworld.com
Ward
Tim
T
Ashcroft
Linda
L
Morris
Julie
J
Heighway
Jim
J
Thatcher
Nick
N
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000077143:Docetaxel; D004720:Endonucleases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016685:Mitomycin / Q000008:administration & dosage; D009367:Neoplasm Staging; D018307:Neoplasms, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D043823:Taxoids; D000077143:Docetaxel; D016685:Mitomycin; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin; D007069:Ifosfamide