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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: Prigge, Elena-Sophie (Author) , Tóth, Csaba (Author) , Dyckhoff, Gerhard (Author) , Freier, Kolja (Author) , Plinkert, Peter K. (Author) , Hoffmann, Jürgen (Author) , Vinokurova, Svetlana (Author) , Knebel Doeberitz, Magnus von (Author) , Reuschenbach, Miriam (Author)
Format: Article (Journal)
Language:English
Published: 2015
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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Summary: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.
Item Description:Im Titel ist „INK4a“ hochgestellt
Published online: 7 Aug 2014
Gesehen am 11.08.2017
Physical Description:Online Resource
ISSN:1097-0215
DOI:10.1002/ijc.29130

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