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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of the cellular p53 tumour-suppressor protein was examined in 78 epidermal tumours, including basal and squamous cell carcinomas, keratoacanthomas, solar keratoses, Bowen's disease and viral warts. An immunohistochemical study was employed using the antibody CM-1, raised against recombinant human p53 protein. Positive staining for p53, not detectable in normal cells because wild-type p53 is rapidly degraded, reflects abnormal stabilization of p53 protein, and in many cases suggests p53 gene mutation. p53 immunoreactivity was not observed in normal skin or in viral warts. In contrast, positive staining for CM-1 was seen throughout the tumour in the majority of basal and squamous cell carcinomas and in Bowen's disease. Immunoreactivity to p53 was also observed in the majority of keratoacanthomas and solar keratoses, but was confirmed to areas of dysplastic basal epithelium. This study demonstrates that accumulation of p53 protein, suggestive in many cases of p53 gene mutation and hence loss of tumour-suppressor function, may occur as an important early step in the development of diverse epidermal cancers.
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PMID:Aberrant expression of p53 tumour-suppressor protein in non-melanoma skin cancer. 146 84

To investigate whether the high frequency of human papillomavirus infection in butchers may be linked to their higher than average incidence of lung cancer, we have examined lung cancers from 40 butchers and 26 controls for the presence of DNA from both HPV type 7, which is found almost uniquely in hand warts from butchers and fishermen, and for those HPV types associated with laryngeal and genital cancers. No HPV 7, and only a low frequency of HPV DNA was found, suggesting that HPV infection does not make an important contribution to the elevated levels of lung cancer in meat handlers. In addition, the frequency of p53 mutation was shown to be slightly lower than previously reported in lung cancers.
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PMID:Human papillomavirus DNA and TP53 mutations in lung cancers from butchers. 764 Feb 8

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

The p53 protein is the product of a tumour suppressor gene, which is implicated in many human malignancies. p53 expression was investigated by immunohistochemistry in a series of viral warts (n = 12) from five patients with epidermodysplasia verruciformis (EV), using a monoclonal anti-p53 antibody (DO7). p53 expression was also investigated in a series of common warts (n = 8), flat warts (n = 8), and penile bowenoid papulosis (n = 6) from non-EV patients. Immunostaining was positive in 11 of 12 (92%) EV warts, whereas p53 reactivity was negative in most cases of warts from non-EV patients. Exons 5-8 of the p53 gene were screened by the polymerase chain reaction-single strand conformation polymorphism technique in four EV warts, which were strongly stained for p53, and p53 mutations were not detected. These results suggest an association between p53 accumulation (probably of wild type) and EV warts.
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PMID:p53 protein expression in viral warts from patients with epidermodysplasia verruciformis. 874 64

Recent data suggest an inverse correlation between human papillomavirus (HPV) infection and p53 tumor-suppressor gene mutation. In an attempt to elucidate the role of p53 mutations in cervical neoplasias, 65 cervical lesions, ranging from normal to malignant, were examined for overexpression of p53 protein by immunohistochemistry in paraffin-embedded tissue, and correlated with proliferating cell nuclear antigen (PCNA). An overexpression was seen in 35% of well-differentiated and 32.5% of poorly-differentiated squamous carcinomas, in 43.33% of microinvasive and 21.66% of CIS. More than 50% of neoplastic cells were immunoreactive for p53 protein in 10% of well-differentiated squamous carcinomas. Other positive specimens showed reactivity in < 24% of tumor cells. No staining was found in adenocarcinoma, dysplastic tissue, condylomas and normal tissue (83.07%). In contrast PCNA was detected in all cases of invasive squamous carcinomas, adenocarcinoma, CIS, CIN III, in 32.5% of CIN II, in 29.54% CIN I, and in 53.52% of wart. More than 50% of tumor cells showed nuclear staining for PCNA protein in 61.17% of invasive squamous carcinomas, in 21.66% of CIS, in 39% CIN III, in 32.5% CIN II and in 7.64% of wart. In the remain cases the positivity of nuclear staining was < 24%. No staining was present in 20% of cases including in normal cervix. Our data suggest that the viral-host protein interactions result in loss of the negative growth control normally exerted by p53. The consequence of HPV infection is a loss of functional wild-type p53 protein within the cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunohistochemical analysis of p53 oncoprotein and proliferating cell nuclear antigen (PCNA) in the cervix uteri. 791 Jan 35

Renal allograft recipients suffer from a markedly increased susceptibility to premalignant and malignant cutaneous lesions. Although various aetiological factors have been implicated, little is known of the associated genetic events. In this study we initially employed immunocytochemical techniques to investigate the prevalence and localisation of accumulated p53 in over 200 cutaneous biopsies (including 56 squamous cell carcinomas) from renal allograft recipients and immunocompetent controls. In renal allograft recipients accumulated p53 was present in 24% of uninvolved skin samples, 14% of viral warts, 41% of premalignant keratoses, 65% of intraepidermal carcinomas and 56% of squamous cell carcinomas [squamous cell carcinoma and intraepidermal carcinoma differed significantly from uninvolved skin (P < 0.005) and viral warts (P < 0.01)]. A similar trend was revealed in immunocompetent patients (an older, chronically sun-exposed population) but with lower prevalence of p53 immunoreactivity: 25% of uninvolved skin samples, 0% of viral warts, 25% of keratoses, 53% of intraepidermal carcinomas and 53% of squamous cell carcinomas. These differences were not statistically significant. Morphologically, p53 immunoreactivity strongly associated with areas of epidermal dysplasia and the abundance of staining correlated positively with the severity of dysplasia. These data suggest that p53 plays a role in skin carcinogenesis and is associated with progression towards the invasive state. No correlation was observed between accumulated p53 and the presence of human papillomavirus (HPV) DNA in any of the lesions. Single-strand conformational polymorphism analysis (exons 5-8) was used to determine the frequency of mutated p53 in 28 malignancies with varying degrees of immunopositivity. p53 mutations were found in 5/9 (56%) malignancies with p53 staining in > 50% of cells, reducing to 1/6 (17%) where 10-50% of cells were positively stained and none where < 10% of cells were stained. These data imply that factors other than p53 gene mutation play a part in accumulation of p53 in skin cancers.
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PMID:Accumulation of p53 is associated with tumour progression in cutaneous lesions of renal allograft recipients. 791 13

Reported are oral mucosal warts (HPV common antigen-positive) from 7 adult HIV+ patients in which there was cytologic atypia and disordered growth. Lesions were papillary, white to red in color, and were located on the lip, gingiva, palate, tongue, and buccal mucosa. Histologically, the keratinocytes in the lesions exhibited atypical features in the form of hyperchromatism and karyomegaly. Koilocytes were frequently seen in the upper level keratinocytes where HPV common antigen was identified. The dysplastic areas, which ranged from mild to severe, typically showed abrupt limiting margins. All lesions exhibited intense PCNA reactivity from basement membrane to surface. Nuclei of mid-level and basal keratinocytes of 3 specimens stained positively for p53 protein. We believe that the atypia found in these lesions represents cytologic change that has malignant potential. The subtype of the HPV in these lesions has not yet been determined.
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PMID:HPV-associated epithelial atypia in oral warts in HIV+ patients. 796 24

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.
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PMID:Immunohistochemical detection of p53 protein in cutaneous lesions from transplant recipients harbouring human papillomavirus DNA. 805 56

It has been proposed that wild-type p53 cell-regulating functions are annulled in human cervical carcinomas, either by mutations in the human papillomavirus (HPV)-negative cases or as a consequence of their complexing with HPV E6. The aim of this study was to test this hypothesis on 39 fresh cervical biopsies by p53 immunocytochemistry (ICC) with antibody PAb 240 and with NISH (non-isotopic in situ hybridization) and PCR (polymerase chain reaction) for HPV detection. p53 protein was present in the basal layer of pure wart virus infection; the basal to middle third of CIN (cervical intraepithelial neoplasia); in 19/22 (86 per cent) HPV-positive cervical carcinomas, ten of which contained integrated HPV; and in 4/8 (50 per cent) HPV-negative cervical carcinomas. Dual detection of p53 antigen and HPV 16 DNA in the same sections demonstrated either p53 protein or integrated HPV 16 alone in the majority of cells. Co-localization of both signals was only evident in isolated cells. These data suggest that PAb 240 immunoreactivity is not mutant-specific. They are, however, consistent with the conformation hypothesis which proposes that wild-type p53 changes from a suppressor (PAb 240-negative) to a promoter (PAb 240-positive) form during cell growth response. Hence, according to this hypothesis, p53 protein expression may represent either the wild-type promoter form or mutant p53 protein, both of which share the same conformation. This may explain co-localization of p53 and HPV in some tumours. However, the absence of p53 protein in 50 per cent HPV-negative squamous cell carcinomas suggests that not all HPV-negative tumours accumulate p53 protein.
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PMID:p53 antigen in cervical condylomata, intraepithelial neoplasia, and carcinoma: relationship to HPV infection and integration. 822 52

Transplant recipients successively develop benign, premalignant and malignant skin lesions on sun-exposed areas. It has been suggested that UV radiations might induce mutations in ras oncogenes and p53 tumour-suppressor gene, responsible for skin cancers. With PCR and oligoprobe hybridization, we investigated c-Ha-ras gene mutations at codons 12 and 61 in 120 cutaneous lesions from grafted patients, since they could represent a marker of the evolution of benign skin lesions towards malignancy in this population; 29 similar skin biopsies from non-immunosuppressed patients were also analyzed. In transplant recipients, we detected mutations at codon 12 only in 1/42 non-melanoma skin cancers and 2/29 pre-cancerous keratoses. No mutation was detected in 11 cases of cutaneous Bowen's disease from grafted patients and in pre-malignant and malignant skin samples from control patients. Benign warts exhibited an overall incidence of 18% and 15% of mutations at codon 12 of c-Ha-ras gene in grafted and control patients respectively. We detected only one mutation at codon 61 in a plantar wart. Human papillomaviruses (HPV) are thought to be involved in the malignant evolution of cutaneous disorders in transplant recipients and cooperate with a ras oncogene to induce malignancy in vitro. The presence of HPV DNA in our series of skin samples from grafted patients showed no correlation with the occurrence of c-Ha-ras mutations. Our findings indicate that c-Ha-ras-gene activation by mutations is rare in cutaneous lesions from transplant recipients, and is unlikely to play a crucial role in transformation towards malignancy in skin carcinogenesis among grafted patients.
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PMID:Low incidence of c-Ha-ras gene mutations in benign and malignant cutaneous lesions from transplant recipients. 825 28


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