title: Expression of p14ARF, p16INK4a and p53 in relation to HPV in (pre-)malignant squamous skin tumours.
abstract: 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 beta-papilloma virus (beta-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 beta-PV types were detected. We found no significant association between p14, p16 or p53 protein expression and overall presence of beta-PV, irrespective of immune status. There was a significant association between presence of beta-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, beta-PV together with ultraviolet radiation act synergetic in promoting carcinogenesis.
authors.affiliation: Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.|Department of Pathology, Canisius Wilhelmina Hospital, Weg door Jonkerbos, Nijmegen, The Netherlands.
authors.forename: Heidi V N
authors.initials: HVN
authors.lastname: Küsters-Vandevelde
authors.affiliation: DDL Diagnostic Laboratory, Fonteynenburglaan, Voorburg, The Netherlands.
authors.forename: Maurits N C
authors.initials: MNC
authors.lastname: de Koning
authors.affiliation: Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Willem J G
authors.initials: WJG
authors.lastname: Melchers
authors.affiliation: DDL Diagnostic Laboratory, Fonteynenburglaan, Voorburg, The Netherlands.
authors.forename: Wim G V
authors.initials: WGV
authors.lastname: Quint
authors.affiliation: Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Peter C M
authors.initials: PCM
authors.lastname: de Wilde
authors.affiliation: Department of Dermatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Elke M G J
authors.initials: EMGJ
authors.lastname: de Jong
authors.affiliation: Department of Dermatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Peter C M
authors.initials: PCM
authors.lastname: van de Kerkhof
authors.affiliation: Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Willeke A M
authors.initials: WAM
authors.lastname: Blokx
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D006801:Humans; D027383:Papillomaviridae / Q000302:isolation & purification*; D011230:Precancerous Conditions / Q000378:metabolism* / Q000821:virology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000821:virology; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53