Journalartikel

Jahr der Veröffentlichung: 2015

Seiten: 1589-1599

Zeitschrift: International Journal of Cancer

Bandnummer: 136

Heftnummer: 7

ISSN: 0020-7136

eISSN: 1097-0215

Open Access Status: Bronze

DOI Link: https://doi.org/10.1002/ijc.29130

Verlag: Wiley

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.

Harvard-Zitierstil: Prigge, E., Toth, C., Dyckhoff, G., Wagner, S., Mueller, F., Wittekindt, C., et al. (2015) p16^INK4a/Ki-67 co-expression specifically identifies transformed cells in the head and neck region, International Journal of Cancer, 136(7), pp. 1589-1599. https://doi.org/10.1002/ijc.29130

APA-Zitierstil: Prigge, E., Toth, C., Dyckhoff, G., Wagner, S., Mueller, F., Wittekindt, C., Freier, K., Plinkert, P., Hoffmann, J., Vinokurova, S., Klussmann, J., Doeberitz, M., & Reuschenbach, M. (2015). p16^INK4a/Ki-67 co-expression specifically identifies transformed cells in the head and neck region. International Journal of Cancer. 136(7), 1589-1599. https://doi.org/10.1002/ijc.29130