title: Effusion immunocytochemistry as an alternative approach for the selection of first-line targeted therapy in advanced lung adenocarcinoma.
abstract: BACKGROUND
  Tumor tissue is often not obtainable or suitable for molecular-based epidermal growth factor receptor (EGFR) mutational analysis in advanced non-small-cell lung cancer (NSCLC). This retrospective and single-institution study was conducted to evaluate the role of effusion immunocytochemistry using two EGFR mutant-specific antibodies for the detection of relevant EGFR mutations in NSCLC, along with the selection of candidates for first-line therapy with EGFR tyrosine kinase inhibitors (TKIs).
  
  
  METHODS
  Immunocytochemistry using two antibodies binding specifically to the major forms of mutant EGFR, L858R, and E746-A750 deletion (delE746-A750), was performed on cell blocks of malignant pleural effusion (MPE) from 78 patients with lung adenocarcinoma, who received first-line EGFR TKIs. The yield of EGFR-mutation detection and prediction of response rate and progression-free survival to TKI treatment by immunocytochemistry were compared with those by clinical characteristics and EGFR sequencing using cell-derived RNA from MPEs.
  
  
  RESULTS
  Of the 78 MPE samples, direct sequencing using cell-derived RNA identified L858R mutation in 42 cases, deletions in exon 19 in 12 cases (delE746-A750 in eight cases), other types of mutations in three cases, and wild-type EGFR in 21 cases. Effusion immunocytochemistry with these two mutant-specific antibodies exhibited a sensitivity of 71% and 88% and a specificity of 86% and 96% for identifying predefined L858R and delE746-A750 mutations, respectively. Effusion immunocytochemistry provided a superior prediction of tumor response and progression-free survival to first-line EGFR TKIs than did clinical characteristics like sex and smoking status. Patients whose effusion immunocytochemistry showed a reaction to either of the two antibodies had a comparable TKI response rate (67% versus 72%) to those with EGFR mutations assessed by direct sequencing from cell-derived RNA.
  
  
  CONCLUSIONS
  Effusion immunocytochemistry could be introduced into clinical practice to identify more NSCLC patients likely to have benefit from first-line TKI treatment, especially for those without adequate tissue for molecular-based EGFR analysis.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Tzu-Hsiu
authors.initials: TH
authors.lastname: Tsai
authors.forename: Shang-Gin
authors.initials: SG
authors.lastname: Wu
authors.forename: Yih-Leong
authors.initials: YL
authors.lastname: Chang
authors.forename: Chen-Tu
authors.initials: CT
authors.lastname: Wu
authors.forename: Meng-Feng
authors.initials: MF
authors.lastname: Tsai
authors.forename: Pin-Fei
authors.initials: PF
authors.lastname: Wei
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Yang
authors.forename: Chong-Jen
authors.initials: CJ
authors.lastname: Yu
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
authors.forename: Jin-Yuan
authors.initials: JY
authors.lastname: Shih
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000813:Anilides / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004252:DNA Mutational Analysis / Q000379:methods; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D009154:Mutation; D011743:Pyrimidines / Q000627:therapeutic use; D012334:RNA, Neoplasm / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; C561722:EGFR tyrosine kinase inhibitor 324674; D011743:Pyrimidines; D012334:RNA, Neoplasm; D066246:ErbB Receptors