Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Functional disturbance of p53 tumor suppressor protein contributes to uncontrolled cell growth. Human papillomavirus (HPV) E6 oncoproteins bind to wild-type p53 and abrogate its function. Our objective was to elucidate the relation of aberrant p53 protein expression to HPV DNA and cellular atypia in male genital warts and premalignant lesions. Immunohistochemically detectable p53 protein expression was studied in 35 male anogenital warts with low-level or no keratinocyte atypia (histologically confirmed condylomata acuminata), in 25 lesions with bowenoid papulosis (BP; carcinoma in situ) histology, and in 10 non-condyloma lesions using immunostaining with three established antibodies recognizing full-length wild-type accumulated p53 protein, or its conformational mutants. HPV DNA specific for HPV 6/11, 16/18, or 31/33/35 was identified by in situ hybridization or by polymerase chain reaction (PCR) - based amplification. Both nuclear and cytoplasmic keratinocyte immunostaining for p53 protein was detected in 41% of condylomata with no keratinocyte atypia and in 42% of condylomata with slight nuclear atypia or with bowenoid papulosis histology. No association of aberrant p53 expression with any specific HPV type or with HPV DNA was observed. Normal skin and some other penile dermatoses were negative for p53 immunostaining. In the follow-up biopsies of 16 BP patients, treated with CO2 laser, recurrence of atypia was seen exclusively in lesions initially positive for both HPV DNA and p53 protein. Our results show that a few cells in male genital warts even with no cellular atypia may express abnormally sequestered or loss-of-function p53 protein, and that concomitant presence of any type of HPV DNA is associated with recurrencies or progression of premalignant changes.
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PMID:Relation of p53 tumor suppressor protein expression to human papillomavirus (HPV) DNA and to cellular atypia in male genital warts and in premalignant lesions. 765 76

Mutations of the tumor-suppressor gene p53 are common in epithelial tumors. Clonal mutations of p53 have been found in cervical and vulvar carcinomas negative for human papillomavirus (HPV), though at least in cervical cancer HPV infection and p53 mutations are not mutually exclusive. We have previously shown that about 40% of male genital warts and bowenoid papulosis lesions exhibit immunohistochemically detectable aberrant p53 protein, irrespective of the presence of HPV DNA. We studied p53 mutations in exons 4-8 with SSCP and sequencing in 13 male patients with 1 to 3 therapy-resistant genital warts or intra-epithelial neoplasias each and in 4 patients with penile squamous cell carcinoma. Thus, 13 genital warts, 6 bowenoid papulosis, 1 Queyrat's erythroplasia and 1 carcinoma in situ were studied. p53 protein was detected immunohistochemically, and HPV status was analyzed with DNA in situ hybridization and amplification of HPV-specific DNA. There was no correlation between p53 protein expression and HPV status. No mutations in exons 5-8 of the p53 gene were found in any of the lesions, and furthermore, no exon 4 mutations were found in lesions positive in p53 immunohistochemistry. In conclusion, overexpression of p53 does not indicate a p53 mutation in male genital warts, pre-malignant lesions or malignant squamous cell carcinomas. Our study thus suggests that p53 mutations are not important, or at least not early, events in male genital carcinogenesis.
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PMID:Absence of p53 mutations in benign and pre-malignant male genital lesions with over-expressed p53 protein. 968 97