title: Quantification of epidermal growth factor receptor (EGFR) mutation may be a predictor of EGFR-tyrosine kinase inhibitor treatment response.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) gene mutation is a reliable predictive factor for response to EGFR-tyrosine kinase inhibitors (TKIs). The quantified EGFR value may also predict response and survival within an EGFR mutated group.
  
  
  METHODS
  We conducted a retrospective study of 836 lung cancer patients. The patient sample was divided into two groups based on the mean delta cycle threshold (∆Ct) value. EGFR mutation tests using peptide nucleic acid (PNA)-mediated clamping polymerase chain reaction (PCR) were performed. The efficiency of PCR clamping was determined by measuring the Ct value and EGFR quantification was determined by the corrected ∆Ct value.
  
  
  RESULTS
  EGFR mutation positivity was 30.1% and there were 235 single activating mutations. In this mutation group, the higher corrected ∆Ct value (≥ mean value) group showed better objective response (70.9% vs. 54.9%, P = 0.022) and clinical benefit rates (86.4% vs. 68.3%, P = 0.003) than the lower group. In addition, corrected ∆Ct values were significantly and inversely correlated with disease response (r = -0.184, P = 0.017). In multivariate analysis, both female gender (P = 0.014) and higher corrected ΔCt value (P = 0.012) were independent predictive factors for better clinical benefit rate. The higher corrected ΔCt value group had a tendency for longer progression-free survival than the lower group (P = 0.050).
  
  
  CONCLUSIONS
  The corrected ∆Ct value, which refers to EGFR quantification by PNA-mediated PCR clamping, can predict better clinical response to EGFR-TKI therapy. However, further study is warranted to determine its value as a biomarker to reflect survival.
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Ha Young
authors.initials: HY
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Hyung Joo
authors.initials: HJ
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Ki-Hyun
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.|Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Jeonnam, Korea.
authors.forename: Tae-Ok
authors.initials: TO
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.|Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Jeonnam, Korea.
authors.forename: Cheol-Kyu
authors.initials: CK
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Shin
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.|Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Jeonnam, Korea.
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Lim
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Kwon
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea. droij@chonnam.ac.kr.|Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Jeonnam, Korea. droij@chonnam.ac.kr.
authors.forename: In-Jae
authors.initials: IJ
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Yu-Il
authors.initials: YI
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Sung-Chul
authors.initials: SC
authors.lastname: Lim
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.|Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Jeonnam, Korea.
authors.forename: Young-Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Jeonnam, Korea.|Department of Pathology, Chonnam National University Medical School, Gwangu, Korea.
authors.forename: Yoo-Duk
authors.initials: YD
authors.lastname: Choi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Epidermal growth factor receptor; lung cancer; peptide nucleic acid; polymerase chain reaction