Universität zu Köln

Mooren, Jeroen J., Gultekin, Sibel E., Straetmans, Jos M. J. A. A., Haesevoets, Annick, Peutz-Kootstra, Carine J., Huebbers, Christian U., Dienes, Hans P., Wieland, Ulrike, Ramaekers, Frans C. S., Kremer, Bernd, Speel, Ernst-Jan M. and Klussmann, Jens P. (2014). P16(INK4A) immunostaining is a strong indicator for high-risk-HPV-associated oropharyngeal carcinomas and dysplasias, but is unreliable to predict low-risk-HPV-infection in head and neck papillomas and laryngeal dysplasias. Int. J. Cancer, 134 (9). S. 2108 - 2118. HOBOKEN: WILEY. ISSN 1097-0215

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Abstract

Human papillomavirus (HPV) is a risk factor for the development of benign and malignant mucosal head and neck lesions. P16(INK4A) is often used as a surrogate marker for HPV-infection, although there is still controversy with respect its reliability. Our aim was to determine if P16(INK4A) overexpression can accurately predict both high-risk and low-risk-HPV-presence in (pre)malignant and benign head and neck lesions. P16(INK4A) immunohistochemistry was performed on paraffin-embedded tissue sections of 162 oropharyngeal squamous cell carcinomas (OPSCC), 14 tonsillar and 23 laryngeal dysplasias, and 20 tonsillar and 27 laryngeal papillomas. PCR, enzyme-immunoassay and FISH analysis were used to assess HPV-presence and type. Of the 162 OPSCC and 14 tonsillar dysplasias, 51 (31%) and 10 (71%) were HPV16-positive, respectively. All tonsillar papillomas were HPV-negative and four laryngeal dysplasias and 26 laryngeal papillomas were positive for HPV6 or -11. P16(INK4A) immunohistochemistry revealed a strong nuclear and cytoplasmic staining in 50 out of 51 HPV16-positive and 5 out of 111 HPV-negative OPSCC (p<0.0001) and in all HPV16-positive tonsillar dysplasias, whereas highly variable staining patterns were detected in the papillomas and laryngeal dysplasias, irrespective of the HPV-status. In addition, the latter lesions generally showed a higher nuclear than cytoplasmic P16(INK4A) immunostaining intensity. In conclusion, our data show that strong nuclear and cytoplasmic p16INK4A overexpression is a reliable surrogate indicator for HPV16 in OPSCC and (adjacent) dysplasias. For HPV6 or -11-positive and HPV-negative benign and premalignant lesions of the tonsil and larynx, however, P16(INK4A) immunostaining is highly variable and cannot be recommended to predict HPV-presence.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mooren, Jeroen J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gultekin, Sibel E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Straetmans, Jos M. J. A. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Haesevoets, Annick UNSPECIFIED UNSPECIFIED UNSPECIFIED Peutz-Kootstra, Carine J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Huebbers, Christian U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dienes, Hans P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wieland, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Ramaekers, Frans C. S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kremer, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Speel, Ernst-Jan M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Klussmann, Jens P. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-440351
DOI:	10.1002/ijc.28534
Journal or Publication Title:	Int. J. Cancer
Volume:	134
Number:	9
Page Range:	S. 2108 - 2118
Date:	2014
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1097-0215
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language IN-SITU HYBRIDIZATION; SQUAMOUS-CELL CARCINOMA; P16 PROTEIN; EXPRESSION; OVEREXPRESSION; DNA; INTEGRATION; LESIONS; P53; IDENTIFICATION Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44035