title: Nuclear translocation of β-catenin and decreased expression of epithelial cadherin in human papillomavirus-positive tonsillar cancer: an early event in human papillomavirus-related tumour progression?
abstract: OBJECTIVE
  High-risk human papillomaviruses (HPVs) constitute an important risk factor for tonsillar cancer. This study describes changes in cell adhesion molecules during metastasis of HPV-related and HPV-unrelated tonsillar carcinomas.
  
  
  RESULTS
  We examined 48 primary tonsillar carcinoma samples (25 HPV-16 DNA-positive, 23 HPV-16 DNA-negative) and their respective lymph node metastases for their HPV status and for the expression of p16, epithelial cadherin (E-cadherin), β-catenin, and vimentin. A positive HPV-specific polymerase chain reaction finding correlated significantly with p16 overexpression in both primary tumours and their metastases (P<0.0001 for both). In HPV-unrelated carcinomas, the expression of E-cadherin was significantly lower in metastases than in primary tumours (P<0.001). In contrast, the expression of nuclear β-catenin was significantly higher in metastases than in primary tumours (P=0.016). In HPV-related carcinomas, nuclear localization of β-catenin expression was already apparent in primary tumours (P=0.030). The expression of vimentin significantly correlated with the grading of the primary tumour (P=0.021).
  
  
  CONCLUSIONS
  Our data indicate that the down-regulation of E-cadherin and the up-regulation of nuclear β-catenin expression might be crucial steps during tumour progression of tonsillar carcinomas, being already present in primary tumours in HPV-driven carcinomas, but becoming apparent in HPV-unrelated tumours later in the process of metastasis.
authors: Department of Otorhinolaryngology, Head and Neck Surgery, School of Medicine, University Hospital of Cologne, Cologne, Germany. markus.stenner@uk-koeln.de
authors: Markus
authors: M
authors: Stenner
authors: Basima
authors: B
authors: Yosef
authors: Christian U
authors: CU
authors: Huebbers
authors: Simon F
authors: SF
authors: Preuss
authors: Hans-Peter
authors: HP
authors: Dienes
authors: Ernst-Jan M
authors: EJ
authors: Speel
authors: Margarete
authors: M
authors: Odenthal
authors: Jens P
authors: JP
authors: Klussmann
mesh_terms: D021581:Active Transport, Cell Nucleus; D000328:Adult; D000368:Aged; D015820:Cadherins / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000556:secondary* / Q000821:virology; D002467:Cell Nucleus / Q000378:metabolism*; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000378:metabolism / Q000473:pathology*; D014067:Tonsillar Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015820:Cadherins; D051176:beta Catenin