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

Markus Stenner*, Basima Yosef, Christian U. Huebbers, Simon F. Preuss, Hans-Peter Dienes, Ernst-Jan M. Speel, Margarete Odenthal, Jens P. Klussmann

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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), beta-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 beta-catenin was significantly higher in metastases than in primary tumours (P = 0.016). In HPV-related carcinomas, nuclear localization of beta-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 beta-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.
Original languageEnglish
Pages (from-to)1117-1126
JournalHistopathology
Volume58
Issue number7
DOIs
Publication statusPublished - Jun 2011

Keywords

  • HPV
  • metastasis
  • nuclear beta-catenin
  • p16
  • tonsillar cancer

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