Expression of p14ARF, p16INK4a and p53 in relation to HPV in (pre‐)malignant squamous skin tumours

• Published in: Journal of cellular and molecular medicine Vol. 13; no. 8b; pp. 2148 - 2157
• Main Authors: Küsters‐Vandevelde, Heidi V.N., de Koning, Maurits N.C., Melchers, Willem J.G., Quint, Wim G.V., de Wilde, Peter C.M., de Jong, Elke M.G.J., van de Kerkhof, Peter C.M., Blokx, Willeke A.M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2009; John Wiley & Sons, Inc
• Subjects: (pre‐)malignant squamous skin lesions; Carcinogenesis; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - virology; Cell cycle; Cervical cancer; Cloning; Contingency tables; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; Dysplasia; Genotyping; HPV; Human papillomavirus; Humans; Immune status; Immunocompetence; INK4a protein; Kidney transplantation; Kidney transplants; Melanoma; Molecular Medicine; P14; p16; p16 Protein; p53; p53 Protein; Papillomaviridae - isolation & purification; Paraffin; Patients; Precancerous Conditions - metabolism; Precancerous Conditions - virology; Renal cell carcinoma; Risk factors; Skin cancer; Skin diseases; Skin lesions; Skin Neoplasms - metabolism; Skin Neoplasms - virology; Squamous cell carcinoma; Tumor Suppressor Protein p14ARF - metabolism; Tumor Suppressor Protein p53 - metabolism; Tumors; Ultraviolet radiation; Netherlands
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/j.1582-4934.2008.00452.x

Studies in cervical dysplasia have reported overexpression of the tumour suppressors p14 and p16 – and absence of p53 – in high‐risk human papilloma virus (HPV)‐ associated lesions. In skin carcinogenesis, the relation between these tumour suppressors and HPV remain unclear. We evaluated the expression of the tumour suppressors p14, p16 and p53 in pre‐malignant and malignant squamous skin tumours, and its relation with risk factors for skin carcinogenesis (HPV, immune status and sun exposure). We performed immunohistochemical stainings for p14, p16 and p53 on paraffin embedded material of 71 pre‐malignant squamous skin lesions and 34 squamous cell carcinomas, from 52 renal transplant recipients (RTRs) and 53 immunocompetent individuals. PCR‐based assays were used for detection and genotyping of β‐papilloma virus (β‐PV) types and mucosal HPV types. P14 expression was independent of the expression of p16 and p53, irrespective of immune status and skin site. In 49 of 105 specimens (46.6%), one or more β‐PV types were detected. We found no significant association between p14, p16 or p53 protein expression and overall presence of β‐PV, irrespective of immune status. There was a significant association between presence of β‐PV and lesions from sun‐exposed skin sites in the RTRs (P= 0.002). We conclude that in skin carcinogenesis, relations between the herein studied tumour suppressors and HPV are different from what one would expect based on findings in cervical neoplasia. P14, p16 and p53 expressions are independent of immune status. Our data indicate that in immunosuppressed patients, β‐PV together with ultraviolet radiation act synergetic in promoting carcinogenesis.