title: Membranous expression of Her3 is associated with a decreased survival in head and neck squamous cell carcinoma.
abstract: BACKGROUND
  Head and neck squamous cell carcinoma (HNSCC) still remains a lethal malignancy benefiting from the identification of the new target for early detection and/or development of new therapeutic regimens based on a better understanding of the biological mechanism for treatment. The overexpression of Her2 and Her3 receptors have been identified in various solid tumors, but its prognostic relevance in HNSCC remains controversial.
  
  
  METHODS
  Three hundred eighty-seven primary HNSCCs, 20 matching metasis and 17 recurrent HNSCCs were arrayed into tissue microarrays. The relationships between Her2 and Her3 protein expression and clinicopathological parameters/survival of HNSCC patients were analyzed with immunohistochemistry.
  
  
  RESULTS
  Her3 is detected as either a cytoplasmic or a membranous dominant expression pattern whereas Her2 expression showed uniform membranous form. In primary tumor tissues, high membranous Her2 expression level was found in 104 (26.9%) cases while positive membranous and cytoplasmic Her3 expression was observed in 34 (8.8%) and 300 (77.5%) samples, respectively. Membranous Her2 expression was significantly associated with histological grade (P = 0.021), as grade 2 tumors showed the highest positive expression. Membranous Her3 over-expression was significantly prevalent in metastatic tissues compared to primary tumors (P = 0.003). Survival analysis indicates that membranous Her3 expression is significantly associated with worse overall survival (P = 0.027) and is an independent prognostic factor in multivariate analysis (hazard ratio, 1.51; 95% confidence interval, 1.01-2.23; P = 0.040).
  
  
  CONCLUSIONS
  These results suggest that membranous Her3 expression is strongly associated with poor prognosis of patients with HNSCC and is a potential candidate molecule for targeted therapy.
authors.affiliation: Tissue Array Research Program, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Takikita
authors.forename: Ran
authors.initials: R
authors.lastname: Xie
authors.forename: Joon-Yong
authors.initials: JY
authors.lastname: Chung
authors.forename: Hanbyoul
authors.initials: H
authors.lastname: Cho
authors.forename: Kris
authors.initials: K
authors.lastname: Ylaya
authors.forename: Seung-Mo
authors.initials: SM
authors.lastname: Hong
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Moskaluk
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000912:Antibodies, Neoplasm / Q000276:immunology; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D002462:Cell Membrane / Q000378:metabolism*; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000276:immunology / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000912:Antibodies, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C508053:ERBB2 protein, human