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

Recent evidence suggests that squamous cell carcinoma of the vulva may have more than one etiology, with only some tumors associated with human papillomavirus (HPV). Cells infected with HPV produce a viral protein (E6) which binds to and causes rapid degradation of p53, possibly contributing to cellular transformation. In several human malignancies, point mutations of p53 alter activity of the p53 protein contributing to cellular transformation. We tested, for the first time, the possibility that HPV-negative tumors of the vulva may have a high incidence of inactivating mutations of p53; while HPV-containing vulvar tumors rarely would have p53 mutations. Twenty-one tumors of the vulva were evaluated for the presence of HPV sequences by amplication with the polymerase chain reaction (PCR) and Southern blotting. These were evaluated for p53 mutations by single strand conformation polymorphism and sequencing of PCR products. HPV DNA sequences were found in 12 of 21 (57%) cancers of the vulva; only one of these 12 (8%) HPV-positive samples had a missense mutation of p53. In contrast, four of nine (44%) HPV-negative vulvar tumors had point mutations of p53. The p53 mutations were found in only metastatic lesion and the only recurrent tumor samples suggesting that the acquisition of p53 mutations may be associated with neoplastic progression. In conclusion, alterations in p53 activity appear to be important in the development of carcinoma of the vulva.
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PMID:Carcinoma of the vulva: HPV and p53 mutations. 818 60

Basic research in vulvar cancer results in new prognostic variables such as human papillomavirus DNA and epidermal growth factor receptor level. It also suggests that p53 mutants are involved in the pathogenesis of this disease. However, histopathological parameters of the lymph nodes, such as capsule breakthrough are the most significant prognosticators for patient survival.
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PMID:Prognostic factors in squamous cell cancer of the vulva and the implications for treatment. 877 55

Clinical and experimental evidence is consistent with a key role of point mutations of the p53 tumor suppressor gene in the etiology of squamous cell carcinoma. To determine the relation of tumor behavior and patient survival in vulvar cancer in regard to p53 status, we retrospectively analyzed 38 paraffin-embedded specimens of primary vulvar cancer for genetic alterations of exons 5-8 of the p53 gene. For detection of p53 point mutations we used in vitro amplification by polymerase chain reaction (PCR) and temperature gradient gel electrophoresis (TGGE) and, as a detection method, direct sequencing for mutation verification. p53 point mutations were detected in 12/38 tumor specimens. Patients bearing p53 point mutations showed a significantly shorter relapse-free (log-rank test, P = 0.002) and overall survival time (log-rank test, P = 0.0006). We conclude that PCR-TGGE is an appropriate method for detection of p53 point mutations in paraffin-embedded material. We show that loss of wild-type p53 is an adverse prognostic factor in patients suffering from vulvar cancer.
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PMID:Detection of p53 point mutations in primary human vulvar cancer by PCR and temperature gradient gel electrophoresis. 899 54

Chromosomal cytogenetic abnormalities are common in tumor cells and are often the basis for more detailed chromosomal mapping of tumor suppressor and oncogenes. Chromosome 11 abnormalities are frequently recognized in various neoplasms. We report a case of Bowen disease (squamous cell carcinoma in situ) of the vulva with an isolated 11p cytogenetic abnormality. A chromosome 11 paint confirmed two copies of chromosome 11 in all analyzed metaphases. An 11p subtelomeric probe confirmed an abnormality of 11p15-->pter indicative of a deletion. Previous studies of invasive vulvar cancers also frequently show 11p cytogenetic abnormalities, but never as an isolated finding. The patient suffered from other diseases that may also be related to this locus. Breakage and p53 studies were normal. It is possible that an 11p abnormality in Bowen's disease is a precursor in the evolution of invasive vulva cancer.
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PMID:Chromosome 11 abnormalities in Bowen disease of the vulva. 907 94

HPV (human papillomavirus) plays an important role in cervical cancer and may also play a role in vulvar cancer. TP53 mutation is common in a variety of cancers but its role in vulvar cancer is not well established. The aim of this study was to assess the prevalence of HPV infection and TP53 mutation as well as their correlation in vulvar cancer. Also, HPV detection and abnormal p53 expression were assessed in relation to age, co-existing vulvar intraepithelial neoplasia and vulvar dystrophy. Forty-eight samples of vulvar cancer were studied. DNA was extracted from formalin-fixed paraffin embedded tissue for polymerase chain reaction/Southern blot study with HPV 16 and 18 and L1 primers. Paraffin sections were immunostained (IHS) for p53 protein using three antibodies, p1801, CM1 and DO7. The p53 mutation was also screened using polymerase chain reaction (PCR) single-stranded conformation polymorphism (SSCP) and confirmed by sequencing. Overall, HPV was detected in 48% (23/48), of which 96% (22/23) were HPV 16 or 18. By IHS, p53 overexpression was detected in 46% of cases whilst TP53 mutations were identified in 21%. In HPV positive and negative tumours, p53 abnormal expression was detected in 39% and 52%, respectively, and TP53 mutation was found in 22% and 20%, respectively. Mutations were mainly found at codons 273 and 204. Age was not found to be associated with HPV detection. However, the presence of HPV (71%) or absence of abnormal p53 expression (65%) were higher in tumours with VIN3, but were not correlated with dystrophy.
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PMID:Abnormal expression or mutation of TP53 and HPV in vulvar cancer. 1044 3

The aim of this research was to detect new valid prognostic indicators that allow us to choose the best therapy and follow-up for patients with a poor prognosis. One hundred and twenty-nine patients with invasive squamous carcinoma of the vulva treated at the Gynecology Clinic of the University of Padua between January 1, 1975 and December 31, 1999 have been evaluated: Protein p53 and ki-67 were studied by immunohistochemical investigations and their prognostic significance was evaluated. The relation with the classic clinico-pathological prognostic factors was also studied. The results showed a close association between tissue overexpression of the two proteins and clinico-pathological characteristics of the aggressivity of the neoplasm. Moreover, the group of positive p53 patients with a diffuse distribution pattern of ki-67 resulted in having a somewhat shorter survival with respect to the groups with negative p53 and/or a focal pattern. Such negative prognostic significance was confirmed by the results of the multivariate analysis performed with the Cox model which shows that patients with p53 positive values and a diffuse pattern have a higher relative risk of death compared to patients with p53 negative values and focal pattern (p=0.0001). The statistical significance of the prognostic value of the association of p53 and ki-67 thus seems to give these two factors greater weight with respect to the others we investigated.
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PMID:Prognostic value of protein p53 and ki-67 in invasive vulvar squamous cell carcinoma. 1119 37

Human papillomavirus is a risk factor for vulvar cancer, whereas human papillomavirus-negative late onset vulvar carcinoma is associated with the dermatologic condition, lichen sclerosus. Human papillomavirus E6 protein targets TP53 for degradation and by inference it has been assumed that human papillomavirus-negative vulvar cancer is dependent upon the acquisition of p53 somatic mutations and subsequent allelic loss. To investigate this, TP53 expression, loss of heterozygosity, and p53 genomic sequence were examined in 29 cases of human papillomavirus-negative vulvar carcinoma with adjacent lichen sclerosus. We examined 37 cases of lichen sclerosus without vulvar carcinoma, 10 cases of nongenital lichen sclerosus, and 12 cases of normal vulvar epithelium served as controls. TP53 was evident in 72% of vulvar carcinoma, 48% in epithelium adjacent to vulvar carcinoma, but was minimal in normal samples. When lichen sclerosus cases were selected to exclude samples with absolutely no TP53 expression through probable failed antigen retrieval or homozygous p53 loss the number of epithelial cells expressing TP53 increased progressively from nongenital lichen sclerosus to lichen sclerosus without vulvar carcinoma, then to lichen sclerosus with vulvar carcinoma (p<0.0001). These data suggest elevated TP53 is a feature of vulvar lichen sclerosus. Seventy-four percent of vulvar carcinoma had chromosome 17p-linked loss of heterozygosity, whereas 47% of adjacent lichen sclerosus featured loss of heterozygosity, but only 31% of vulvar carcinoma had p53 mutations, a frequency less than reported previously. Seven percent of adjacent lichen sclerosus had mutations, showing for the first time the presence of an identical mutation to the matched vulvar carcinoma. These data, however, implicate p53 mutations as a later event in vulvar carcinoma and in marked contrast to the original expectation, our loss of heterozygosity data are consistent with loss of another locus (not p53) on 17p operating as a tumor suppressor in lichen sclerosus destined to develop vulvar carcinoma.
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PMID:Overexpression of wild-type p53 in lichen sclerosus adjacent to human papillomavirus-negative vulvar cancer. 1244 88

Vulvar carcinoma accounts for 3-5% of all genital cancers. The most common histology of vulvar cancer is squamous cell carcinoma. It has been suggested that vulvar cancer exists as two separate diseases--HPV-positive, occurring in young women, and p53-positive, that occurs in older women. As extensive surgery resection is gold standard of treatment, it is important to play attention for all symptoms, suggesting the beginning of disease. Understanding of the anatomy and the mechanism of lymphatic spread have made modifications in surgical technique possible, allowing less radical excisions.
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PMID:[Can vulvar carcinoma be a danger in the 21st century?]. 1599 47

On the basis of varying morphology and pathogenesis, two types of vulvar intraepithelial neoplasias (VIN) have been defined: the common type (approximately 98%), classic VIN, is characterised by strong association to high-risk HPV infection (up to 90%), occurrence at younger age (median age 30-40 years) and multifocality. The differentiated (or simplex) type is rare (1%-2%) and is associated with older age (median age 65 years) and p53 alterations. It is usually diagnosed in combination with vulvar (keratinizing) squamous cell carcinoma. The classification currently preferred by the WHO in which VIN are classified into VIN 1-3 is to be replaced due to new data and according to a proposal by the International Society for the Study of Vulvovaginal Diseases (ISSVD) which eliminates VIN 1 and combines VIN 2 and 3 to VIN of common or, depending on histopathology, differentiated type. Prognostically relevant factors in vulvar cancer include stage of disease, inguinal lymph node involvement, size of metastatic deposits and presence of extracapsular extension, depth of invasion and distance of the tumor from resection margins. Tumor grade and the presence of lymphovascular space involvement are controversially discussed.
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PMID:[Pathoanatomical preparation and reporting of specimens from precancerous lesions and carcinomas of the vulva]. 1913 58

Vulvar carcinoma is a rare female genital neoplasia. Radical surgery, which has been the standard treatment approach, is often accompanied by considerable morbidity. To reduce the incidence of complications there has been a movement toward individualised therapy and less radical surgery. Associated with this, new tumour markers that could serve as prognostic indicators would be of considerable value to guide treatment decision. In this review, a brief update of molecular pathological markers of vulvar carcinomas is provided, and their impact as prognostic markers is addressed. p16, p21, p14, p27, cyclin A, cyclin D1, p53, vascular endothelial growth factor (VEGF), transforming growth factor alpha, HER-2 and epidermal growth factor receptor (EGFR) have been found to be important in the pathogenesis and/or progression of vulvar carcinomas. Furthermore, human papillomavirus, p16, p21, p14, p53, VEGF, CD44v3, CD44v6, CD44v4, CD44v9, CD44v10, HER-2, EGFR, matrix metalloproteinase-12, caspase 3, Bcl-2 and nm23-H1 have been correlated to clinical outcome of patients with vulvar carcinomas. However, due to the relative small number of studies reported for each molecular pathological marker, and the relative small number of vulvar carcinomas included and the lack of multivariate analysis in the majority of these studies, no conclusion regarding the prognostic value of these markers can be drawn. Therefore, the investigated markers have not yet earned a place in standard clinical diagnostics or treatment, and further studies are needed to clarify the clinical value of these markers.
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PMID:A review of molecular pathological markers in vulvar carcinoma: lack of application in clinical practice. 1925 52


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