Nuclear translocation of β-catenin and decreased expression of E-cadherin in HPV-positive tonsillar cancer: An early event in HPV-related tumor progression?

Markus Stenner (1) , Basima Yosef (2) , Christian U Huebbers (3) , Simon Florian Preuss (4) , Hans Peter Dienes (2) , Ernst-Jan M Speel (5) , Margarete Odenthal (2) , Jens Peter Klussmann (6)

1 ENT
2 Pathology
3 Jean-Uhrmacher-Institute
4 ENT
5 Molecular Cell Biology
6 ENT

Aims: High-risk human papillomaviruses (HPV) seem to be an important risk factor for tonsillar cancer. However, only few data exist concerning molecular changes during metastasis. 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, E-cadherin, β-catenin and vimentin. A positive HPV-specific PCR correlated significantly with p16 overexpression in both the primary tumor and metastasis (p<0.0001 both). In HPV-unrelated patients the expression of E-cadherin was significantly less abundant in metastases than in primary tumors (p<0.001). The expression of nuclear β-catenin was contrariwise significantly higher in metastases than in primary tumors (p=0.016). Compared to HPV-unrelated patients, in HPV-related ones the nuclear localisation of β-catenin expression was already apparent in primary tumors (p=0.030). The expression of vimentin significantly correlated with the grading of the primary tumor (p=0.021). Conclusions: Our data newly indicate that the downregulation of E-cadherin together with an upregulation of nuclear β-catenin might be crucial steps during tumor progression of tonsillar cancer being already present in primary tumors in HPV driven cancers but become apparent in HPV-unrelated tumors later during the process of metastasizing.

Mots clés: Medicine

Markus Stenner, Basima Yosef, Christian U Huebbers, Simon Florian Preuss, Hans Peter Dienes, et al.. Nuclear translocation of β-catenin and decreased expression of E-cadherin in HPV-positive tonsillar cancer: An early event in HPV-related tumor progression?. Histopathology, 2011, 58 (7), pp.1117. ⟨10.1111/j.1365-2559.2011.03805.x⟩. ⟨hal-00626292⟩