title: Increased p16CDKN2A protein within feline cutaneous viral plaques, bowenoid in situ carcinomas, and a subset of invasive squamous cell carcinomas.
abstract: Cutaneous viral plaques and bowenoid in situ carcinomas (BISCs) in cats are thought to be caused by papillomavirus (PV) infection. There is evidence that PVs may also cause some feline invasive squamous cell carcinomas (ISCCs). Human oncogenic PVs degrade retinoblastoma (RB) protein, impairing cell cycle control. Loss of RB function also increases p16(CDKN2A) protein (p16), and increased p16 immunoreactivity within a human oral ISCC indicates that the neoplasm was caused by PV infection. In the present study, p16 immunoreactivity was evaluated in 14 feline viral plaques, 14 BISCs, 7 non-solar-induced ISCCs, 11 solar-induced ISCCs, and 14 trichoblastomas. Increased p16 was present within all viral plaques, BISCs, and non-solar-induced ISCCs. In contrast, little p16 immunoreactivity was visible in the solar-induced ISCCs or trichoblastomas. PV DNA was consistently amplified from viral plaques, BISCs, and non-solar-induced ISCCs. However, just 5 solar-induced ISCCs and 1 trichoblastoma contained PV DNA. Given that both increased p16 immunoreactivity and PV DNA were present within viral plaques, BISCs, and non-solar-induced ISCCs, all 3 may be caused by PV infection. This suggests that feline non-solar-induced ISCCs may develop as a result of neoplastic progression from viral plaques and BISCs. Whether PVs promote this progression is unknown; however, evidence from this study suggests the PV that is associated with viral plaques and BISCs is able to disrupt the p16-RB pathway and therefore could have oncogenic potential. Immunohistochemical detection of p16 appears to be a useful technique to investigate the role of PVs in feline skin disease.
authors.affiliation: Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand. J.Munday@massey.ac.nz
authors.forename: J S
authors.initials: JS
authors.lastname: Munday
authors.forename: A F
authors.initials: AF
authors.lastname: French
authors.forename: J
authors.initials: J
authors.lastname: Peters-Kennedy
authors.forename: G M B
authors.initials: GM
authors.lastname: Orbell
authors.forename: K
authors.initials: K
authors.lastname: Gwynne
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D002371:Cat Diseases / Q000378:metabolism* / Q000473:pathology* / Q000821:virology*; D002415:Cats; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D007150:Immunohistochemistry / Q000662:veterinary; D009361:Neoplasm Invasiveness / Q000473:pathology*; D030361:Papillomavirus Infections / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D016160:Retinoblastoma Protein / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein