title: Tyrosine1248-phosphorylated HER2 expression and HER2 gene amplification in female invasive ductal carcinomas.
abstract: BACKGROUND
  Phosphorylated HER2 (pHER2) may more accurately reflect the signaling and functional activity of the HER2 protein than detection of HER2 itself. The detection of HER2 gene amplification using fluorescence in situ hybridization (FISH) provides superior prognostic information for the diagnosis of breast cancer. However, the relationship between pHER2 expression in tissue samples and HER2 gene amplification remains unclear.
  
  
  METHODS
  A total of 210 cases were recruited. The expression of HER2 and tyrosine (Tyr)1248-pHER2 was investigated by immunohistochemistry, and HER2 gene amplification was analyzed by FISH. Spearman's rank correlation test was employed to confirm correlation between HER2 and Tyr1248-pHER2. Chi-square and Student's t test were used to determine a significant difference between the baseline characteristics of tumors and the FISH, HER2 and Tyr1248-pHER2 results. The phosphorylation rate of HER2 was calculated using a digital-analysis system.
  
  
  RESULTS
  HER2 expression was significantly (P < 0.001) associated with Tyr1248-pHER2 expression. HER2 gene amplification could be detected in 55 (26.2%) of the 210 tumors; 40 were HER2 positive and 32 were Tyr1248-pHER2 positive. The sensitivity and specificity of HER2 and Tyr1248-pHER2 for HER2 gene amplification were 72.7 and 58.2%, and 91.6 and 95.5%, respectively. In cases with an HER2 score of 2, and a phosphorylation score of 2 or 3, gene amplification was observed in 4 (80.0%) out of 5 tumors.
  
  
  CONCLUSIONS
  Tyr1248-pHER2 expression is highly specific for HER2 gene amplification. The phosphorylation status might provide an adjunct to the assessment of gene amplification in patients with an HER2 score of 2.
authors.affiliation: Institute for Clinical Research, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, 3-1 Aoyama-cho, Kure 737-0023, Japan. taniyamak@kure-nh.go.jp
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Taniyama
authors.forename: Katsunari
authors.initials: K
authors.lastname: Ishida
authors.forename: Tamaki
authors.initials: T
authors.lastname: Toda
authors.forename: Junichi
authors.initials: J
authors.lastname: Motoshita
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kuraoka
authors.forename: Akihisa
authors.initials: A
authors.lastname: Saito
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Tani
authors.forename: Toshinori
authors.initials: T
authors.lastname: Uike
authors.forename: Seiichi
authors.initials: S
authors.lastname: Teramoto
authors.forename: Masato
authors.initials: M
authors.lastname: Koseki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D010766:Phosphorylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D014443:Tyrosine