p16(INK4a) /Ki-67 co-expression specifically identifies transformed cells in the head and neck region.

Abstract

p16(INK4a) immunohistochemical overexpression is an overall reliable surrogate marker of human papillomavirus (HPV)-associated head and neck squamous cell carcinomas (HNSCC). However, cases of ambiguous p16(INK4a) overexpression are regularly detected in the head and neck: p16(INK4a) expression can be observed in non-malignant tissue, such as tonsillar crypt epithelium and a proportion of branchial cleft cysts. Additionally, diverse patterns of p16(INK4) expression can complicate interpretation of "p16(INK4a) -positivity". These aspects impede the unrestricted application of p16(INK4a) as a diagnostic marker in the head and neck. We hypothesized that combined detection of p16(INK4a) and the proliferation marker Ki-67 could support clarification of ambiguous p16(INK4a) expression in the head and neck by specifically indicating p16(INK4a) -expressing cells with proliferative activity. p16(INK4a) /Ki-67 co-expression in a combined staining procedure was correlated to distinct p16(INK4a) 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. p16(INK4a) /Ki-67 co-expression only occurred in transformed cells of the head and neck. Co-expression was never detected in non-transformed cells. Combined p16(INK4a) /Ki-67 expression was stringently associated with a diffuse p16(INK4a) expression pattern. All HPV oncogene-expressing HNSCC showed p16(INK4a) /Ki-67 co-expression. We demonstrate that p16(INK4a) /Ki-67 co-expression occurs exclusively in transformed cells of the head and neck. Our findings indicate a substantial impact of combined p16(INK4a) /Ki-67 expression in the assessment of ambiguous p16(INK4a) expression in the head and neck by specifically identifying p16(INK4a) -expressing cells with proliferative activity. This property will be of considerable significance for head and neck histo- and cytopathology.

• Authors: 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, Miriam Reuschenbach
• Journal: International journal of cancer (Int J Cancer) Vol. 136 Issue 7 Pg. 1589-99 (Apr 01 2015) ISSN: 1097-0215 [Electronic] United States
• PMID: 25104331 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 UICC.

Chemical References

• Biomarkers, Tumor
• Cyclin-Dependent Kinase Inhibitor p16
• DNA, Viral
• E6 protein, Human papillomavirus type 16
• Ki-67 Antigen
• Oncogene Proteins, Viral
• Repressor Proteins

Topics

• Biomarkers, Tumor (genetics)
• Carcinoma, Squamous Cell (diagnosis, genetics, virology)
• Cell Line, Transformed
• Cyclin-Dependent Kinase Inhibitor p16 (genetics, metabolism)
• DNA, Viral (genetics)
• Gene Expression
• Head and Neck Neoplasms (diagnosis, genetics, virology)
• Humans
• Immunohistochemistry
• Ki-67 Antigen (genetics, metabolism)
• Oncogene Proteins, Viral (genetics, metabolism)
• Papillomaviridae (genetics)
• Papillomavirus Infections (complications)
• Repressor Proteins (genetics, metabolism)
• Squamous Cell Carcinoma of Head and Neck