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

Studies using cervical carcinoma cell lines usually show mutated p53 in cases without detectable HPV, and wild-type p53 in cases with detectable HPV. These findings suggest that loss of p53 function, either by mutation or by binding to HPV E6, is required for cervical carcinogenesis. Because mutated p53 is usually detectable immunohistochemically, one would predict an inverse relationship between the presence of HPV and detectable p53. In this study we examined 88 formalin-fixed paraffin-embedded clinical specimens of cervix for the presence of HPV and p53 expression. All cases were studied for the presence of p53 using immunohistochemical methods. The antibody used was mouse monoclonal PAb1801 (Biogenex). The presence of HPV was detected by PCR. Twenty-six specimens showed foci of p53 expression (0/7 normal, 1/8 (13%) condylomas, 1/6 (17%) CIN I, 3/7 (43%) CIN II, 6/20 (30%) CIN III, 13/22 (59%) SCC, 2/5 (40%) adenosquamous carcinomas, and 0/13 adenocarcinomas). p53 expression was more frequent in SCC than with CIN (P = 0.026). HPV was present in 15 of 24 cases with detectable p53 and 22 of 48 cases without detectable p53. No correlation was seen between HPV status and detection of p53. With the exception of one case, p53 expression was seen in less than 10% of cells. p53 expression was not detected in any of the 13 adenocarcinomas examined (P = 0.0016 vs SCC). Our results show that alterations of p53 may play a role in the pathogenesis of cervical squamous carcinoma. However, p53 expression was neither sufficient nor required for cervical carcinogenesis, irrespective of HPV status.
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PMID:Cervical squamous dysplasias and carcinomas with immunodetectable p53 frequently contain HPV. 767 94

The data on the etiological factors presented here may enable us to suggest a synergism between the various factors associated with the pathogenesis of cervical cancer. Infection of the cervix by HPV 16/18 may result in persistence of viral DNA. The persistent HPV-DNA undergoes disruption at the E2 region, when integrated into the host genome. The transcriptional products E6 and E7 oncoproteins bind to and cause the degradation of p53 and Rb tumor-suppressor gene products. It is possible that, at that point, other cofactors may be involved in the progression toward a precancerous or cancerous condition. Those cofactors may include cigarette smoking, by introducing co-carcinogens to the tissue or by suppressing the local or systemic immune resistance similar to the effect of depressed immune resistance seen in AIDS or immunosuppression of transplant patients; hormones, by enhancing growth of HPV and transformation of HPV infected cells; low serum vitamin levels leading to decreased tissue resistance; or other infections causing local inflammation and the production of free radicals. CIN develops, leading eventually to cervical cancer.
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PMID:Etiology of cervical cancer: current concepts. 773 27

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

The E6 protein of the high-risk human papillomavirus (HPV) types 16 and 18 is capable of complexing with the wild-type p53 tumor suppressor gene product, leading to loss of the normal p53 function as an anti-oncogene, whereas the low-risk HPV types 6 and 11 lack this binding property. The malignant potential of HPV 16 and 18 has been ascribed to this complexing of E6 with p53, which regularly leads to undetectable expression of the latter in HPV-positive lesions. To assess the role of p53 in HPV-associated genital carcinogenesis, the expression of p53 protein was studied immunohistochemically in 22 genital carcinomas and precancer lesions; 8 vulvar carcinomas, 1 VIN (vulvar intraepithelial neoplasia), 5 cervical carcinomas and 8 CIN (cervical intraepithelial neoplasia) using monoclonal antibody PAb 1801. Presence of HPV was demonstrated by PCR using HPV consensus primers, and amplified HPV-DNA was digested with the restriction enzymes giving distinct patterns for various HPV-types in gel electrophoresis. HPV-typing was confirmed by in situ hybridization with biotinylated DNA probes. Altogether, 17 of the 22 specimens (77%) showed p53 expression: 67% of the precancer lesions and 83% of carcinomas. Expression was more frequent (89%) in the vulvar than (70%) in cervical lesions. Using PCR,HPV DNA was detected in 19/22(86%) of the samples. The following HPV types were identified: HPV 6 (2 samples), HPV 11 (3 cases), HPV 16 (5 cases), HPV 33 (3 cases), and 6 contained unidentified HPV types. All HPV DNA-negative specimens showed p53 expression. Of the 19 HPV DNA-positive lesions, 5 were p53-negative, three of these being HPV 16 positive CIN lesions. The remaining two HPV 16 lesions were invasive carcinomas with a weak p53 expression. HPV 6 and 11-positive lesions showed a weak p53 expression more frequently than HPV-negative cases and HPV 33 lesions. The results indicate that p53 expression is detectable, but it is less frequent and less intense in HPV DNA-positive genital precancer lesions and carcinomas (particularly those with HPV 16 DNA) as compared with HPV DNA-negative lesions.
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PMID:Expression of p53 protein related to the presence of human papillomavirus (HPV) DNA in genital carcinomas and precancer lesions. 839 70

The significant changes over the last decade in the CIN/cervical carcinoma area have involved the increasing recognition of many cervical carcinomas as adenocarcinomas, rather than squamous cell type, and their propensity for arising in young women. Another area of interest is the deployment of new molecular techniques that are unveiling the role of oncogene co-factors (e.g. HPV, p53) in the biologic evolution of CIN and hopefully glandular dysplasia.
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PMID:The pathology of cervical cancer. 861 76

The usefulness of prognostic factors in gynecological cancer was evaluated using the oncogenes, tumor suppressor genes and DNA viruses detected with the molecular biological technique. In uterine cervical cancer, HPV types 16 and 18 are considered to have a high oncogenic risk, and are commonly associated with high grade CIN and invasive cancer under persistent HPV infection. C-myc overexpression in advanced stage and p53 mutation in HPV negative case are associated with poor survival. In endometrial cancer, oncogene activation and expression are less frequent than in cervical and ovarian cancer. K-ras point mutation (codon 12) tumors are more aggressive and c-erbB-2 overexpression are associated with metastasis and poor survival. In ovarian cancer, there are numerous abnormalities of oncogenes and tumor suppressor genes. Especially, EGF-R and PDGF-R alpha expression are associated with decreased survival. p53 mutation also decreases survival and response to chemotherapy. Recently. MSH2 (Lynch II syndrome) and BRCA1 gene are known to relate with familial ovarian cancer.
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PMID:[Evaluation of prognostic factors in gynecological cancer examined by molecular biological study]. 868 14

To study the molecular abnormalities involved in the multistage development of cervical carcinoma (CC), we investigated the presence of oncogenic human papillomavirus (HPV) sequences, loss of heterozygosity (LOH), and microsatellite alterations at several genes/loci at 3p (3p14.2 at the FHIT gene, 3p14.3-21.1, 3p21, and 3p22-24.2), 9p21, RB and P53, and P53 gene point mutations in precisely microdissected archival tissues from 20 CCs and their accompanying precursor lesions (cervical intraepithelial neoplasia, CIN; n = 40) and normal epithelia (n = 20). In all HPV-positive cases (90% of CCs), HPV sequences were detected as the earliest appearing molecular change or simultaneously with other changes. LOH at any 3p region was found in 70% of CCs, and 3p14.2 (FHIT gene/FRA3B fragile site) (56%) and 3p21 (57%) were the most frequent 3p sites of loss. LOH at some 3p region was in the CIN I stage, and the 3p deletions in precursor CIN lesions were smaller than the 3p losses found in the associated invasive CC. LOH at the other regions studied and P53 gene mutations were less frequent and later events. Microsatellite alterations were detected in 35% of CCs, and identical abnormalities were detected in the associated precursor lesions. Although infection with oncogenic HPV strains is the earliest and most frequent molecular event, progressive deletions at one or more 3p regions (particularly at 3p14.2, and 3p21) are also frequent events occurring early in the pathogenesis of CC.
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PMID:Deletions of chromosome 3p are frequent and early events in the pathogenesis of uterine cervical carcinoma. 924 43

Early epidemiological studies of cervical neoplasia suggested a causal relation with sexual activity and human papillomaviruses (HPVs) have emerged as prime suspects as venerally transmitted carcinogens. HPVs fall into two broad camps: low risk types, associated with cervical condylomas and CIN 1; and high risk types (mostly 16 and 18), found in 50-80% of CIN 2 and CIN 3 lesions, and 90% of cancers. This association with cancer is very strong, with odds ratios of > 15 (often much higher) in case-control studies that are methodologically sound. An infrequently detected third group of intermediate risk type HPVs is associated with all grades of CIN and occasionally with cancers. HPVs have also been detected in a wide range of asymptomatic controls, indicating that other events are required for development of neoplasia such as viral persistence and/or altered expression of viral genes, often following integration of the viral genome. This leaves the two major viral oncogenes, E6 and E7, directly coupled to viral enhancers and promoters, allowing their continued expression after integration. High risk HPV E7 proteins bind and inactivate the Rb protein, whereas E6 proteins bind p53 and direct its rapid degradation. A range of putative cofactors has been implicated in progression: HLA type, immunosuppression, sex steroid hormones, and smoking; most of these cofactors appear to influence progression to CIN 3. The natural history includes progression to CIN 3 in 10% of CIN 1 and 20% of CIN 2 cases, whereas at least 12% of CIN 3 cases progress to invasive carcinoma. Cervical glandular intraepithelial neoplasia (CGIN) often coexists with squamous CIN, and the premalignant potential of high grade CGIN is not in doubt, but the natural history of low grade CGIN remains uncertain. A high proportion of CGIN lesions and adenocarcinomas are HPV positive, and HPV18 has been implicated more in glandular than in squamous lesions. A strong clinical case for the application of HPV typing of cells recovered from cervical scrapes can be made; however, a rigorous cost-benefit analysis of introducing HPV typing into the cervical screening programme is required. Prophylactic and therapeutic HPV vaccines are under development. This article reviews the aetiology, pathogenesis, and pathology of cervical neoplasia, emphasising the role of HPVs.
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PMID:Aetiology, pathogenesis, and pathology of cervical neoplasia. 960 80

For several years there has been the association between the persistent HPV infection (especially with high oncogenic potency i.e. 16, 18) and the cervical intraepithelial neoplasia. The pathomechanism is probably considered with spread of the early virus gene E1, E2 and the suppressor protein p53 complexes. Further on these complexes cause the neoplastic cell transformation. There has also been described the role of impaired immune response in these cases. The abnormalities cover malformation of antigen presenting system APC, decrease of MHC-I and MHC-II heavy chains rate, decrease of the Langer-hans cells and decrease of count and cytotoxic activities of lymphocytes B and NK cells. The invasive and destructive techniques of HPV associated CIN treatment do not respect its pathogenesis. Therefore the new non surgical methods of treatment would play a major role in treatment and prevention of women especially in their reproductive period. The aim of this work was the evaluation of the Iscador QuS and Intron A role in the management of HPV associated CIN. The 60 patients with CIN and HPV have been diagnosed and treated in our clinic for 12 months. Early results present increase of regression and significant decrease of progression rates in both groups of examined women, comparing to the control group. The stationery state rates in this groups of women were similar to the control group.
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PMID:[Iscador QuS and human recombinant interferon alpha (Intron A) in cervical intraepithelial neoplasia (CIN)]. 1037 35

Oncogenic types of human papilloma virus (HPV) are known to be closely associated with cervical carcinoma. On the other hand, the oncogenic process is associated with various abnormalities in the mechanisms of cellular regulation. In this study, we detected the expressions of p53 and p21 proteins in cervical lesions by immunohistochemical techniques, and examined the relationship with HPV infection as well as the clinical usefulness of the results. Cervical biopsy specimens from 107 cases of cervical lesions were studied. HPV-DNA was detected by the hybrid capture method using probe A for low oncogenic types and probe B for high oncogenic types. Anti p21, anti-p53 antibodies were used to perform immunostaining. Point mutation in the p53 gene was analyzed by the DGGE method. High oncogenic HPV types were detected at high frequencies in CIN and SCC. In lesions associated with high oncogenic HPV, p53 protein was detected in 33.4% of the lesions and p21 protein in 36.3%. The p53 gene was analyzed in all cases, and point mutation was not detected. No relation was detected between HPV infection and p53/p21 protein expression. Since mutation was not found in the p53 gene, the p53 protein expressed was considered to be wild-type, which is suspected to play a role in inhibiting disease progression in some cases.
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PMID:[Relation between human papilloma virus DNA and expressions of p53 and p21 proteins in cervical lesions]. 1063 30


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