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?

Histopathology. 2011 Jun;58(7):1117-26. doi: 10.1111/j.1365-2559.2011.03805.x. Epub 2011 Mar 25.

Abstract

Aims: 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.

Methods and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Adult
  • Aged
  • Cadherins / metabolism*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / secondary*
  • Carcinoma, Squamous Cell / virology
  • Cell Nucleus / metabolism*
  • Disease Progression
  • Down-Regulation
  • Female
  • Humans
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Lymph Nodes / virology
  • Male
  • Middle Aged
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / pathology*
  • Tonsillar Neoplasms / metabolism
  • Tonsillar Neoplasms / pathology*
  • Tonsillar Neoplasms / virology
  • beta Catenin / metabolism*

Substances

  • Cadherins
  • beta Catenin