title: The use of mutation-specific antibodies in predicting the effect of EGFR-TKIs in patients with non-small-cell lung cancer.
abstract: OBJECTIVE
  We aimed to quantify the epidermal growth factor receptor (EGFR) mutation in tumors and to analyze its prediction of EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment efficacy in EGFR mutation-positive non-small-cell lung cancer (NSCLC) patients.
  
  
  METHODS
  We examined EGFR mutation status in 124 lung cancer samples by direct sequencing and amplification refractory mutation system. Among them, 41 were appropriate to quantify the expression of mutant EGFR proteins using immunohistochemistry (IHC) with mutation-specific antibodies. The quantification was determined by both the staining intensity and the proportion of stained tumor cells.
  
  
  RESULTS
  The median progression-free survival (PFS) in patients with a high score for mutant EGFR expression was 18.0 months (95 % CI 16.0-20.0), which was significantly longer than that in patients with a low score (8.0 months; 95 % CI 2.6-13.4; P = 0.048). Such significant association with patients' PFS was also apparent in the proportion of stained tumor cells (median, 19.0 vs. 8.0 months; P = 0.019), but not in the staining intensity (P = 0.787). Among the 41 specimens, 32 were detected EGFR mutation positive by both direct sequencing and ARMS, referring to a relatively high abundance of mutation, and 26 (81.3 %) of them gained a high expression score of mutant proteins as well. Six samples with mutation negative by direct sequencing but positive by ARMS, which showed a low abundance, and 5 (83.3 %) of them also revealed a low expression score. The EGFR mutation quantitative analysis using mutation-specific IHC was moderately consistent with that by molecular-based assays (P = 0.001, kappa value 0.50).
  
  
  CONCLUSIONS
  Our results suggest that immunohistochemical analysis with mutation-specific antibodies is a promising approach for quantifying EGFR mutations, and may predict the effect of EGFR-TKI treatment for EGFR mutation-positive NSCLC.
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, No.180 Fenglin Rd, Shanghai, 200032, China.
authors.forename: Jingya
authors.initials: J
authors.lastname: Zhao
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Xue
authors.forename: Nuo
authors.initials: N
authors.lastname: Xu
authors.forename: Xin
authors.initials: X
authors.lastname: Ye
authors.forename: Haiying
authors.initials: H
authors.lastname: Zeng
authors.forename: Shaohua
authors.initials: S
authors.lastname: Lu
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.forename: Sujie
authors.initials: S
authors.lastname: Akesu
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.forename: Deming
authors.initials: D
authors.lastname: He
authors.forename: Yunshan
authors.initials: Y
authors.lastname: Tan
authors.forename: Qunying
authors.initials: Q
authors.lastname: Hong
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Guanshan
authors.initials: G
authors.lastname: Zhu
authors.forename: Yingyong
authors.initials: Y
authors.lastname: Hou
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000235:genetics / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use
chemical_list: D000906:Antibodies; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors