p16INK4a/Ki-67 co-expression specifically identifies transformed cells in the head and neck region
p16INK4a immunohistochemical overexpression is an overall reliable surrogate marker of human papillomavirus (HPV)-associated head and neck squamous cell carcinomas (HNSCC). However, cases of ambiguous p16INK4a overexpression are regularly detected in the head and neck: p16INK4a expression can be obs...
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| Main Authors: | , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2015
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| In: |
International journal of cancer
Year: 2014, Volume: 136, Issue: 7, Pages: 1589-1599 |
| ISSN: | 1097-0215 |
| DOI: | 10.1002/ijc.29130 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1002/ijc.29130 Verlag, kostenfrei, Volltext: http://onlinelibrary.wiley.com/doi/10.1002/ijc.29130/abstract 
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| Author Notes: | Elena-Sophie Prigge, Csaba Toth, Gerhard Dyckhoff, Steffen Wagner, Franziska Müller, Claus Wittekindt, Kolja Freier, Peter Plinkert, Jürgen Hoffmann, Svetlana Vinokurova, Jens Peter Klussmann, Magnus von Knebel Doeberitz and Miriam Reuschenbach |
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| 245 | 1 | 0 | |a p16INK4a/Ki-67 co-expression specifically identifies transformed cells in the head and neck region |c Elena-Sophie Prigge, Csaba Toth, Gerhard Dyckhoff, Steffen Wagner, Franziska Müller, Claus Wittekindt, Kolja Freier, Peter Plinkert, Jürgen Hoffmann, Svetlana Vinokurova, Jens Peter Klussmann, Magnus von Knebel Doeberitz and Miriam Reuschenbach |
| 246 | 3 | 3 | |a p16 INK4a /Ki-67 co-expression specifically identifies transformed cells in the head and neck region |
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| 520 | |a p16INK4a immunohistochemical overexpression is an overall reliable surrogate marker of human papillomavirus (HPV)-associated head and neck squamous cell carcinomas (HNSCC). However, cases of ambiguous p16INK4a overexpression are regularly detected in the head and neck: p16INK4a expression can be observed in non-malignant tissue, such as tonsillar crypt epithelium and a proportion of branchial cleft cysts. Additionally, diverse patterns of p16INK4 expression can complicate interpretation of “p16INK4a-positivity”. These aspects impede the unrestricted application of p16INK4a as a diagnostic marker in the head and neck. We hypothesized that combined detection of p16INK4a and the proliferation marker Ki-67 could support clarification of ambiguous p16INK4a expression in the head and neck by specifically indicating p16INK4a-expressing cells with proliferative activity. p16INK4a/Ki-67 co-expression in a combined staining procedure was correlated to distinct p16INK4a expression patterns and HPV status (HPV DNA followed by E6*I oncogene mRNA detection) in 147 HNSCC and 50 non-malignant head and neck samples. p16INK4a/Ki-67 co-expression only occurred in transformed cells of the head and neck. Co-expression was never detected in non-transformed cells. Combined p16INK4a/Ki-67 expression was stringently associated with a diffuse p16INK4a expression pattern. All HPV oncogene-expressing HNSCC showed p16INK4a/Ki-67 co-expression. We demonstrate that p16INK4a/Ki-67 co-expression occurs exclusively in transformed cells of the head and neck. Our findings indicate a substantial impact of combined p16INK4a/Ki-67 expression in the assessment of ambiguous p16INK4a expression in the head and neck by specifically identifying p16INK4a-expressing cells with proliferative activity. This property will be of considerable significance for head and neck histo- and cytopathology. | ||
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