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Human Papillomavirus and Overexpression of P16INK4a in Nonmelanoma Skin Cancer

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Background.

P16INK4a overexpression has been identified as a specific biomarker in high-risk human papillomavirus (HPV)–infected cervical (pre)cancer lesions. Objective.

To evaluate the overexpression of this cyclin-dependent kinase inhibitor in skin tumors depending on HPV infections, we analyzed normal skin, benign skin disease, and skin cancer specimens. Methods.

Biopsies of 23 patients with normal histology (3), psoriasis (2), verrucae vulgaris (2), actinic keratoses (5), squamous cell carcinoma (SCC) in situ (3), Bowen's carcinoma (1), and SCC (7) were analyzed. Specimens of 23 patients were immunostained using the monoclonal antibody E6H4 specific for p16INK4a. HPV status was assessed by a polymerase chain reaction (PCR) system to detect all currently known HPV types. MY (MY09/MY11 and MYN9/MYN10)-, CP (CP65/CP70 and CP66/CP69)-nested PCR, and three single PCR methods CN1, CN3, and CN4 were used in a first step, and HPV typing was performed by restriction fragment length polymorphism analysis. Only -globin–positive patients were included in this study. Results.

HPV DNA was detected in all actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC, in 50% (one of two) of verrucae vulgaris, in 66% (two of three) of normal skin, and in none of two psoriasis. P16INK4a expression was not detected in normal skin, psoriasis, and verrucae vulgares. Overexpression of p16INK4a was detected in a subset of dysplastic cells (10% to 80%) of all skin (pre)cancer lesions such as actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC infected with HPV independent of sun exposure. Conclusion.

P16INK4a appears to be overexpressed in a portion of dysplastic cells from actinic keratoses and SCC. Further studies to examine the association of HPV infection and the overexpression of p16INK4a are warranted.

R. RIDDER HAS A FINANCIAL INTEREST IN THE COMPANY THAT DEVELOPS IN VITRO DIAGNOSTIC DEVICES ON THE E6H4 ANTIBODY FOR OTHER TUMOR ENTITIES THAN NMSC.
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Document Type: Research Article

Affiliations: 1: Charité, University of Berlin, Department of Dermatology, Berlin, 2: Institut für Pathologie und Molekularbiologie, Hamburg, and 3: MTM Laboratories AG, Heidelberg, Germany

Publication date: 01 March 2004

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