Commercial laboratory testing of excision repair cross-complementation group 1 expression in non-small cell lung cancer.
Excision repair cross-complementation group 1 (ERCC1) expression by non-small cell lung cancer (NSCLC) has been reported to predict resistance to platinum-based therapies. On this basis, several commercial laboratories have offered ERCC1 testing to facilitate clinical decision making, but the reliability of such assays has recently been called into question. Methods. First, three large commercial laboratories were queried for their cumulative ERCC1 test results in NSCLC patients to compare their independent rates of ERCC1 expression. Second, identical tumor blocks from individual NSCLC patients underwent round-robin analysis to evaluate interlaboratory concordance for ERCC1 expression. Third, a retrospective review of medical records from NSCLC patients identified those who were both highly responsive and resistant to platinum-based chemotherapies. Tumor blocks from these patients were then used in a gold standard analysis to determine individual laboratory sensitivity and specificity for ERCC1 results. Results. Significant differences were observed in independent laboratory ERRC1 expression rates (Clarient 70% vs. Genzyme 60% vs. Third Laboratory 44%, p < .0001 for all two-way comparisons). Only 4 of 18 tumors examined in round-robin analysis were fully concordant (κ ≤ 0.222 for all two-way comparisons). In preselected platinum responsive and resistant specimens, none of these three commercially marketed laboratory assays achieved a specificity of greater than 50%. Conclusion. The results of commercial laboratory testing for ERCC1 are inconsistent and unreliable. Better validation and postmarketing surveillance should be mandated before tumor biomarker assays are allowed to enter the clinical arena.
Department of Medicine, Department of Pathology, and Department of Health Outcomes Research and Biostatistics, State University of New York Health Science Center at Stony Brook, Winthrop-University Hospital, Mineola, New York, USA.
Jeffrey G
JG
Schneider
Nosha
N
Farhadfar
Abirami
A
Sivapiragasam
Matthew
M
Geller
Shahidul
S
Islam
Elena
E
Selbs
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D016190:Carboplatin / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D002945:Cisplatin / Q000627:therapeutic use*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004720:Endonucleases / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics; D012189:Retrospective Studies
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin
ERCC1; Lung cancer; Platinum sensitivity; Tumor predictive biomarker