title: HER2 mRNA status contributes to the discrepancy between gene amplification and protein overexpression in gastric cancer.
abstract: BACKGROUND
  Human epidermal growth factor receptor 2 (HER2) is an important proto-oncogene of prognostic use in gastric cancer (GC). Fluorescence in-situ hybridization (FISH) and immunohistochemistry (IHC) are the main clinical methods of detection of HER2, but consistency between the methods is poor and the cause of the discrepancy is unclear.
  
  
  OBJECTIVE
  To investigate the involvement of HER2 mRNA status in the disparity between gene amplification and protein overexpression.
  
  
  METHODS
  We investigated HER2 gene, mRNA, and protein profiles in gastric precancer and cancer tissues by use of the molecular approaches FISH, real-time polymerase chain reaction, and IHC. The relationships between HER2 and matrix metalloproteinase 9 (MMP9) and Smad7 expression were analyzed and the involvement of HER2 in the interaction between tumor cells and lymphocytes was investigated by coculturing GC cell lines with peripheral blood mononuclear cells (PBMCs).
  
  
  RESULTS
  HER2 protein expression was significantly increased in cancer compared with precancer (P = 0.003), and the corresponding mRNA levels were significantly lower in precancer and cancer tissues than in normal tissues (κ = 0.290, P = 0.025). HER2 mRNA levels were significantly higher in tumor than in peritumor tissue (P = 0.028), and were positively correlated with MMP9 and Smad7 mRNA levels in tumor tissues. HER2 mRNA expression in GC cell lines was increased by coculture with PBMCs.
  
  
  CONCLUSIONS
  Different HER2 mRNA profiles, possibly in relation to contact between tumor cells and lymphocytes, might help to explain the discrepancy between gene amplification and protein overexpression results.
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Fudan University, No. 180, Fenglin Road, Shanghai, 200032, China, mamalailema@163.com.
authors.forename: Gui-Fen
authors.initials: GF
authors.lastname: Ma
authors.forename: Yi-Mei
authors.initials: YM
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Gao
authors.forename: Qing
authors.initials: Q
authors.lastname: Miao
authors.forename: Tian-Cheng
authors.initials: TC
authors.lastname: Luo
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Zeng
authors.forename: Shi-Yao
authors.initials: SY
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008875:Middle Aged; D011237:Predictive Value of Tests; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D051906:Smad7 Protein / Q000235:genetics; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D020780:Matrix Metalloproteinase 9; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D051906:Smad7 Protein; C000715470:MAS1 protein, human; C497806:SMAD7 protein, human; C508053:ERBB2 protein, human; C579270:MMP9 protein, human