title: Implementation and Quality Control of Lung Cancer EGFR Genetic Testing by MALDI-TOF Mass Spectrometry in Taiwan Clinical Practice.
abstract: Molecular diagnostics in cancer pharmacogenomics is indispensable for making targeted therapy decisions especially in lung cancer. For routine clinical practice, the flexible testing platform and implemented quality system are important for failure rate and turnaround time (TAT) reduction. We established and validated the multiplex EGFR testing by MALDI-TOF MS according to ISO15189 regulation and CLIA recommendation in Taiwan. Totally 8,147 cases from Aug-2011 to Jul-2015 were assayed and statistical characteristics were reported. The intra-run precision of EGFR mutation frequency was CV 2.15% (L858R) and 2.77% (T790M); the inter-run precision was CV 3.50% (L858R) and 2.84% (T790M). Accuracy tests by consensus reference biomaterials showed 100% consistence with datasheet (public database). Both analytical sensitivity and specificity were 100% while taking Sanger sequencing as the gold-standard method for comparison. EGFR mutation frequency of peripheral blood mononuclear cell for reference range determination was 0.002 ± 0.016% (95% CI: 0.000-0.036) (L858R) and 0.292 ± 0.289% (95% CI: 0.000-0.871) (T790M). The average TAT was 4.5 working days and the failure rate was less than 0.1%. In conclusion, this study provides a comprehensive report of lung cancer EGFR mutation detection from platform establishment, method validation to clinical routine practice. It may be a reference model for molecular diagnostics in cancer pharmacogenomics.
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.|Departments of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Kang-Yi
authors.initials: KY
authors.lastname: Su
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Jau-Tsuen
authors.initials: JT
authors.lastname: Kao
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Bing-Ching
authors.initials: BC
authors.lastname: Ho
authors.affiliation: Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
authors.forename: Hsuan-Yu
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.|Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Comprehensive Cancer Center, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Gee-Cheng
authors.initials: GC
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chao-Chi
authors.initials: CC
authors.lastname: Ho
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.|Departments of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Center of Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Pathology and Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.|Center for Optoelectronic Biomedicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Sung-Liang
authors.initials: SL
authors.lastname: Yu
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D000066491:Clinical Decision-Making; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods*; D006284:Health Plan Implementation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D009154:Mutation; D017410:Practice Guidelines as Topic / Q000592:standards*; D011446:Prospective Studies; D011786:Quality Control; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D013624:Taiwan; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C512478:EGFR protein, human; D066246:ErbB Receptors