title: Dual surrogate markers for rapid prediction of epidermal growth factor receptor mutation status in advanced adenocarcinoma of the lung: A novel approach in resource-limited setting.
abstract: BACKGROUND
  Tyrosine kinase inhibitors have revolutionized the treatment of metastatic lung cancer in patients with epidermal growth factor receptor (EGFR) mutations. Amplified refractory mutation system (ARMS)-reverse transcription-polymerase chain reaction (RT-PCR), the current standard for detecting EGFR mutation status is time-consuming and highly expensive. Consequently any surrogate test which are cheaper, faster and as accurate as the PCR method will help in early diagnosis and management of patients with lung cancer, especially in resource-limited settings.
  
  
  METHODS
  Eighty-five patients, all of South Indian origin, with adenocarcinoma of lung, registered between October 2009 and January 2013, were evaluated for EGFR mutation status by using scorpion probe based ARMS RT-PCR method. Immunohistochemical (IHC) was performed using the phosphorylated AKT (P-AKT) and thyroid transcription factor-1 (TTF-1) on above patient's sample, and the results were compared with EGFR mutation tests.
  
  
  RESULTS
  EGFR mutation was positive in 34 of 85 patients (40%). P-AKT and TTF-1 were positive in 50 (58.8%) and 68 (80%) patients respectively. Both P-AKT and TTF-1 had statistically significant correlation with EGFR mutation status. Positive and negative predictive value of P-AKT in diagnosing EGFR mutation was 58% and 85.5% and that for TTF-1 was 48.5% and 94.1%, respectively. The problem of low positive predictive value can partly be overcome by testing P-AKT and TTF-1 simultaneously.
  
  
  CONCLUSIONS
  P-AKT and TTF-1 using IHC had statistically significant correlation with EGFR mutation with high negative predictive value. In the case of urgency of starting treatment, EGFR mutation testing may be avoided in those patients who are negative for these IHC markers and can be started on chemotherapy.
authors.affiliation: Department of Medical Oncology, K M C, Manipal, Karnataka, India.
authors.forename: K S
authors.initials: KS
authors.lastname: Udupa
authors.forename: R
authors.initials: R
authors.lastname: Rajendranath
authors.forename: T G
authors.initials: TG
authors.lastname: Sagar
authors.forename: S
authors.initials: S
authors.lastname: Sundersingh
authors.forename: T
authors.initials: T
authors.lastname: Joseph
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D015415:Biomarkers; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D051058:Oncogene Protein v-akt / Q000235:genetics*; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D015415:Biomarkers; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; C512478:EGFR protein, human; D066246:ErbB Receptors; D051058:Oncogene Protein v-akt