title: Human epidermal growth factor receptor 2 (HER2) in salivary gland carcinomas.
abstract: BACKGROUND
  HER2 is a target for antibody-based treatment of breast and gastric carcinoma which is highly successful in advanced disease as well as in the adjuvant setting. To determine the potential applicability of such therapies, salivary gland tumours were analysed for HER2 overexpression/amplification in this study.
  
  
  METHODS
  A tissue microarray (TMA) was constructed from 994 carcinomas and 205 adenomas of the salivary gland. Slides were analysed for HER2 overexpression and gene amplification using FDA approved reagents for immunohistochemistry (IHC; Hercep-Test; Dako) and fluorescence in situ hybridisation (FISH; PathVysion; Vysis-Abbott).
  
  
  RESULTS
  HER2 was found overexpressed in 39 of 915 (4.26%) and amplified in nine of 915 interpretable salivary gland carcinomas (0.98%). HER2 overexpression was mostly found in salivary duct carcinoma. All other entities were mainly HER2 negative. HER2 was overexpressed in 34 of 319 (10.65%) mucoepidermoid carcinomas, one of 170 (0.59%) acinic cell adenocarcinomas and three of 14 (21.43%) salivary duct carcinomas. HER2 amplification was seen in three of 294 (1.01%) mucoepidermoid carcinomas, three of 14 (21.43%) salivary duct carcinomas, one of 81 (1.23%) adenocarcinomas (NOS), one of 12 (8.33%) cystadenocarcinomas and one of 19 (2.08%) myoepithelial carcinomas. HER2 amplification was found in seven of 39 immunohistochemically HER2 positive (2+ and 3+) tumours (17.95%) but in only two of 849 (0.24%) IHC negative tumours (p < 0.0001). No amplification/overexpression was found in adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, polymorphous low grade carcinoma, basal cell carcinoma, myoepithelial carcinoma, cystadenocarcinoma and oncocytic carcinoma.
  
  
  CONCLUSIONS
  HER2 overexpression caused by gene amplification was observed in about 20% of patients with salivary duct cancers but was rare in salivary adenomas and other carcinomas. Therefore, anti-HER2 therapy may represent a therapeutic option only in a small subgroup of salivary gland tumours.
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. t.clauditz@uke.de
authors.forename: Till Sebastian
authors.initials: TS
authors.lastname: Clauditz
authors.forename: Maren
authors.initials: M
authors.lastname: Reiff
authors.forename: Linn
authors.initials: L
authors.lastname: Gravert
authors.forename: Alexander
authors.initials: A
authors.lastname: Gnoss
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Tsourlakis
authors.forename: Adrian
authors.initials: A
authors.lastname: Münscher
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Rainald
authors.initials: R
authors.lastname: Knecht
authors.forename: Waldemar
authors.initials: W
authors.lastname: Wilczak
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human