Immunohistochemical detection of p53 protein in cutaneous lesions from transplant recipients harbouring human papillomavirus DNA.
Human papillomaviruses (HPV) are thought to be involved in the malignant evolution of cutaneous lesions from transplant recipients. As E6 proteins from potentially oncogenic HPV types degrade p53 tumour suppressor gene product in vitro, we analysed p53 protein status in benign, premalignant and malignant skin lesions from grafted patients, to determine whether HPV may interfere with p53 function. With immunohistochemistry, p53 protein accumulation was detected in 70% of skin lesions from grafted patients. p53 immunoreactivity was confined to basal keratinocytes in benign lesions (warts, condylomas), while suprabasal keratinocytes were also stained in premalignant and malignant skin lesions (precancerous keratoses, squamous cell carcinomas). Multiple HPV carriage was detected with in situ hybridization in benign and malignant skin lesions from transplant recipients: low risk HPV types 1, 2, 6, 11 and potentially oncogenic HPV types 5, 16, 18 were frequently found. There was no clear correlation between p53 detection and the presence of the HPV types under study. The frequent detection of p53 protein in cutaneous lesions from grafted patients is suggestive of p53 protein accumulation interfering with normal function. Our results may reflect the presence of mutated p53 proteins due to the mutagenic effect of ultra-violet (UV), or wild-type p53 protein accumulation in response to UV-induced DNA damage, or may be produced by the interaction with HPV-encoded E6 proteins.
Pélisson
I
I
INSERM U346 affiliée CNRS, Hôpital Edouard Herriot, Lyon, France.
Chardonnet
Y
Y
Euvrard
S
S
Schmitt
D
D
D004279:DNA, Viral / Q000302:isolation & purification; D016027:Heart Transplantation; D006801:Humans; D007150:Immunohistochemistry; D016030:Kidney Transplantation; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000821:virology; D011183:Postoperative Complications / Q000821:virology; D011230:Precancerous Conditions / Q000737:chemistry* / Q000821:virology; D012871:Skin Diseases / Q000821:virology; D012878:Skin Neoplasms / Q000737:chemistry* / Q000821:virology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D014412:Tumor Virus Infections / Q000821:virology
D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53