Nuclear translocation of ß-catenin and decreased expression of epithelial cadherin in human papillomavirus-positive tonsillar cancer: an early event in human papillomavirus-related tumour progression?

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), ß-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 ß-catenin was significantly higher in metastases than in primary tumours (P=0.016). In HPV-related carcinomas, nuclear localization of ß-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 ß-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.