title: The diagnostic accuracy of pleural effusion and plasma samples versus tumour tissue for detection of EGFR mutation in patients with advanced non-small cell lung cancer: comparison of methodologies.
abstract: OBJECTIVE
  To evaluate the suitability of malignant pleural effusion (MPE) and plasma as surrogate samples for epidermal growth factor receptor (EGFR) mutation detection, and compare three different detection methods.
  
  
  METHODS
  Matched tissue and plasma samples were collected from patients with advanced non-small cell lung cancer (NSCLC) (stage IIIB/IV adenocarcinoma/adenosquamous carcinoma), with matched MPE samples collected from a subgroup. DNA was extracted from tissue, MPE cell block, MPE supernatant and plasma before mutation detection by amplification refractory mutation system (ARMS) (all samples), Sanger sequencing and mutant-specific immunohistochemistry (IHC) (tissue and MPE cell blocks only).
  
  
  RESULTS
  Sensitivity of MPE cell block, MPE supernatant and plasma versus tissue: 81.8% (9/11), 63.6% (7/11) and 67.5% (27/40); specificity was 80.0% (8/10), 100% (10/10) and 100% (46/46), respectively. Sensitivity of Sanger sequencing versus ARMS: 81.8% (27/33) for tissue, 40% (4/10) for MPE cell blocks; specificity was 100% (36/36 and 12/12) for both. Sensitivity of mutant-specific IHC versus ARMS: 54.8% (17/31) for tissue, 50.0% (6/12) for MPE cell blocks; specificity was 97.1% (34/35) and 100% (14/14), respectively.
  
  
  CONCLUSIONS
  MPE and plasma are valid surrogates for NSCLC tumour EGFR mutation detection when tissue is not available. ARMS is most suitable for mutation detection in tissue and MPE cell blocks; however, mutant-specific IHC could be a complementary method when DNA-based molecular testing is unavailable.
authors.affiliation: Affiliated Hospital of Academy of Military Medical Science, , Beijing, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Liu
authors.forename: Yachao
authors.initials: Y
authors.lastname: Lu
authors.forename: Guanshan
authors.initials: G
authors.lastname: Zhu
authors.forename: Yao
authors.initials: Y
authors.lastname: Lei
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.forename: Haifeng
authors.initials: H
authors.lastname: Qin
authors.forename: Chuanhao
authors.initials: C
authors.lastname: Tang
authors.forename: Gillian
authors.initials: G
authors.lastname: Ellison
authors.forename: Rose
authors.initials: R
authors.lastname: McCormack
authors.forename: Qunsheng
authors.initials: Q
authors.lastname: Ji
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018196:Carcinoma, Adenosquamous / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002681:China; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010949:Plasma; D016066:Pleural Effusion, Malignant / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA
chemical_list: D004273:DNA, Neoplasm; D066246:ErbB Receptors
keywords: Diagnostics; Egfr; Lung Cancer