p16INK4A overexpression is frequently detected in tumour‐free tonsil tissue without association with HPV |
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| Authors: | Boris Klingenberg Harriët C Hafkamp Annick Haesevoets Johannes J Manni Pieter J Slootweg Soenke J Weissenborn Jens P Klussmann Ernst‐Jan M Speel |
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| Institution: | 1. Department of Molecular Cell Biology;2. Department of Otorhinolaryngology, Head and Neck Surgery, GROW‐School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht;3. Present address: Reinier de Graaf Gasthuis, Delft, The Netherlands.;4. Department of Pathology, University Medical Centre Nijmegen, Nijmegen, the Netherlands;5. Institute for Virology;6. Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Cologne, Germany;7. Present address: Universtiy of Giessen, Germany. |
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| Abstract: | Klingenberg B, Hafkamp H C, Haesevoets A, Manni J J, Slootweg P J, Weissenborn S J, Klussmann J P & Speel E‐J M(2010) Histopathology 56, 957–967 p16 INK4A overexpression is frequently detected in tumour‐free tonsil tissue without association with HPV Aims: Oncogenic human papillomavirus (HPV) type 16 has been strongly associated with tonsillar squamous cell carcinoma (TSCC) and appears to be of prognostic significance. Because HPV+ TSCC also accumulates p16INK4A, this cyclin‐dependent kinase inhibitor has been proposed as a potential biomarker for HPV in clinical diagnosis. The aim of this study was to determine the prevalence of HPV in tumour‐free tonsillar tissue and the value of p16INK4A overexpression in predicting its presence. Methods and results: p16INK4A overexpression was detected by immunohistochemistry in tissue sections of tumour‐free tonsils of 262 patients. They were treated for non‐oncological reasons (snoring or chronic/recurrent tonsillitis) consisting of tonsillectomy. Genomic DNA isolated from these tissues was subjected to HPV‐specific polymerase chain reaction (PCR) analysis. p16INK4A immunoreactivity was detected in 28% of samples in both crypt epithelium (49/177) and lymphoid germinal centres (52/187), which correlated with each other (P < 0.0001). No reactivity was observed in superficial squamous cell epithelium. HPV16 and 18 were detected by PCR analysis in 2/195 cases (1%), which, however, were negative on fluorescence in situ hybridization analysis and discrepant on p16INK4A immunostaining. Conclusions: No proof was found for the presence of HPV in tumour‐free tonsil tissue, despite increased p16INK4A expression in a quarter of tonsil cases. Other mechanisms than HPV infection are therefore implicated in p16INK4A up‐regulation. |
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| Keywords: | crypt epithelium human papillomavirus immunostaining normal tonsil p16INK4A polymerase chain reaction tumour‐free tonsil |
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