Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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.
 ...
PMID:Carcinoma of the vulva: HPV and p53 mutations. 818 60

Twenty-five cases of squamous cell carcinoma of the vulva were examined for p53 protein overexpression using immunohistochemistry. p 53 protein overexpression was associated with poorer overall survival.
 ...
PMID:[Overexpression of p53 as prognosis factor in vulvar carcinoma]. 873 23

In this study we have investigated the prevalence of p53 overexpression in various vulvar lesions and its significance as a prognostic parameter in patients with vulvar carcinoma. Overexpression of p53 was studied in 66 patients with squamous cell carcinoma of the vulva and in the following synchronous epithelial lesions: intraepithelial neoplasia grade I (VIN I) (n = 33), VIN II (n = 11), VIN III (n = 16), lichen sclerosus (n = 30), squamous cell hyperplasia (n = 37), normal vulvar skin of patients with vulvar carcinoma (n = 55), and in 18 samples of normal skin from healthy controls. Survival curves of the p53-positive and p53-negative patients were compared using the log-rank test. The use of DO7, and anti-p53 monoclonal antibody, showed p53 overexpression in 35 (53%) specimens of carcinoma, in eight (27%) of lichen sclerosus, in five (14%) of squamous cell hyperplasia, in six (18%) of VIN I, in two (18%) of VIN II, in two (13%) of VIN III, and in seven (13%) specimens of normal vulvar skin. Staining of normal skin from healthy controls showed no p53 positive specimens. No relationship between expression of p53 and disease-free survival in patients with vulvar carcinoma was present. In malignant, synchronous premalignant and non-neoplastic epithelial disorders of the vulva, p53 overexpression is a frequent observation, indicating that the latter two groups have characteristics of premalignant lesions. In addition, p53 overexpression was not a useful prognostic parameter for patients with vulvar carcinoma.
 ...
PMID:p53 protein overexpression, a frequent observation in squamous cell carcinoma of the vulva and in various synchronous vulvar epithelia, has no value as a prognostic parameter. 910 65

The aim of the study was to investigate quantitatively the heterogeneity of vulvar squamous cell carcinoma. The material consisted of archive material from 36 patients with squamous cell carcinoma of the vulva treated at Department of Gynaecology and Oncology. Selected slides were stained with iodidium propide and immunostained for p53 and Ki-67 (MIB-1 clone). Percent of immunopositive nuclei, number of mitotic figures, DNA-ploidy, and geometric nuclear parameters such as area, perimeter, minimum, mean and maximum diameter, shape factor and folding factor were measured with applications running on AnalySIS pro 2.11 (Soft Imaging System GmbH, Germany) image analysis system. Cluster analysis disclosed 2 groups significantly different in respect to patient age, nuclear area, p53 expression and DNA-ploidy. No significant difference in proliferation markers nor clinical stage was found. In other studies also 2 distinct group of squamous cell carcinoma of the vulva are postulated; that groups differ in pathogenesis and epidemiology. Our study confirms this heterogeneity by an independent method. In the present study usefulness of image analysis for separating squamous cell carcinoma of the vulva into distinct groups was explored and proved.
 ...
PMID:Morphometry separates squamous cell carcinoma of the vulva into two distinct groups. 1032 84

To offer more tailored treatment to individual patients with squamous cell carcinoma of the vulva, more accurate prediction of lymph node metastases is required. As p53 and mdm2 are genes known to be involved in the development of other tumours, we studied expression of p53 and mdm2 in carcinogenesis of squamous cell carcinoma of the vulva and their clinical relevance. Archival material of 141 T1 and T2 vulvar tumours were used. Of the 141 primary tumours, the corresponding 39 lymph node metastases (LNM) were studied, and in 90 cases the pre-existent epithelia adjacent to the tumour (EAT) and in 14 cases vulvar intraepithelial neoplasia adjacent to the tumour (VIN) was also investigated. Detection of p53 and mdm2 protein was immunohistochemically performed. Scoring categories were: negative (1); weakly positive (2); moderately to markedly positive (3); and markedly positive (4). Overexpression of p53 was seen in 56% of the LNM, 39% of the primary tumours, 21% of the VIN lesions and 0% in the group of EAT. No relation was found between overexpression of p53 in the primary tumour and LNM. Expression of mdm2 was seen in 14% of the primary tumours, of which four cases were marked positive. In the group of LNM no mdm2-positive staining was observed. In the group of EAT, 25% was mdm2-positive, of which six cases were marked positive. In the group of VIN, 36% showed moderate (score 3) mdm2 expression. No relation was found between expression of mdm2 and LNM. In squamous cell carcinoma, overexpression of p53 is a late event in carcinogenesis. Marked expression of mdm2 is rarely seen in vulvar carcinomas, indicating that aberrant p53 cannot induce mdm2 expression. LNM cannot be predicted by detection of these proteins.
 ...
PMID:In squamous cell carcinoma of the vulva, overexpression of p53 is a late event and neither p53 nor mdm2 expression is a useful marker to predict lymph node metastases. 1038 75

We have sought to determine the basis for preferential loss of the codon 72 proline (72P) rather than the arginine (72R) allele in squamous cell carcinoma of the vulva with loss of heterozygosity (LOH) in p53. The proportion of cases containing human papillomavirus (HPV) 16 was not statistically different among individuals with either 72RR or 72RP in the germ line (P > 0.99), but p53 LOH was significantly more common in individuals heterozygous 72RP than in 72RR individuals (P = 0.04). LOH more commonly involved the 72P allele in both HPV-positive and HPV-negative cancers. Our results imply that preferential loss of the 72P allele in vulval squamous cell carcinoma occurs by HPV-dependent and -independent mechanisms.
 ...
PMID:Preferential retention of codon 72 arginine p53 in squamous cell carcinomas of the vulva occurs in cancers positive and negative for human papillomavirus. 1115 83

Lichen sclerosus (LS) has a known association with the development of squamous cell carcinoma of the vulva. The purpose of this study was to investigate molecular markers, which could indicate premalignant changes. Multiple sequential vulvar biopsies were taken over a period of 11 years from a patient with longstanding LS. Immunohistochemical staining was used to demonstrate a range of molecular markers. Increased expression of p53 and Ki67 was found in areas of squamous hyperplasia (SH) and differentiated vulvar intraepithelial neoplasia (dVIN) which correlated with the subsequent development of invasive squamous cell carcinoma (SCC). Molecular changes have been found to accompany histologic changes in the progression of vulvar LS to malignancy. Such markers may prove a useful addition in the clinical management of these conditions.
 ...
PMID:Cell cycle proteins as molecular markers of malignant change in vulvar lichen sclerosus. 1132 9

Non-neoplastic epithelial lesions of the vulva (NNEDV) lichen sclerosus (LS) and squamous hyperplasia (SH) have been implicated in the pathogenesis of squamous cell carcinoma of the vulva (SCC). To date, there have been no recognisable precursor lesions for SCC associated with NNEDV. TP53 is the most frequent genetic change in human cancers and can indicate both aetiology and molecular pathogenesis of tumours. A total of 27 SCC patients underwent immunohistochemistry (IHC) and TP53 mutational analysis using microdissection and direct sequencing. There were 19 patients with areas of adjacent epidermis: 17 had NNEDV (four SCCs had more than one adjacent lesion) and two had normal epidermis. In all, 70.4% of the SCCs, 40% LS and 22.2% SH demonstrated overexpression of p53. In total, 77.8% of SCCs, 46.7% of LS and 22.2% SH demonstrated mutations in TP53, with the majority of lesions having a mutation in codon 136. Eight cases were identified where the same mutation was identified in the SCC and in the adjacent area. These data suggest that TP53 mutations develop in NNEDV and are intrinsic to the clonal evolution that leads to SCC. The type of mutation detected is more likely to occur due to endogenous cellular changes rather than exogenous carcinogen exposure.
 ...
PMID:TP53 mutations in vulval lichen sclerosus adjacent to squamous cell carcinoma of the vulva. 1467 2

This study was undertaken to examine the expression of p16 and p53 in vulvar intraepithelial neoplasia (VIN) and squamous cell carcinoma (SCC) of the vulva. We also analyzed the relationship between p16 and p53 immunoexpression in women younger vs. older than 55 years of age. Seventyseven histologic samples of vulvar tissue, treated surgically between June 2000 and November 2004 at the Complexo Hospitalar Santa Casa (Porto Alegre, Brazil), were investigated. We analyzed 28 cases of VIN, 37 cases of SCC and 12 normal vulvar tissues. The percentage of immunohistochemical positivity for p16 had the following distribution across the groups: VIN: 21.4% (6/28), cancer: 24.3% (9/37) and control: absent (p=0.202). p53 expression showed the following percentages: VIN: 60.7% (17/28), cancer: 18.9% (7/37) and control: 8.3% (1/12) (p=0.01). p16 expression in the cancer group (mean age: 63.4 years) was positive in 6 and 3 cases of women younger or older than 55 years, respectively (54.5% vs. 11.5%, p=0.01). p53 expression was not detected in young females with cancer, while it was expressed in 7/26 (26.9%) cases of the group of females older than 55 years of age (p=0.08). Our results suggest an increase in the immunohistochemical expression of p16 protein in young women with squamous cell carcinoma of the vulva, and a possible association with a low expression of p53.
 ...
PMID:Immunohistochemical expression of p16 and p53 in vulvar intraepithelial neoplasia and squamous cell carcinoma of the vulva. 1699 95

Pseudoangiosarcomatous squamous cell carcinoma is an unusual but aggressive variant of acantholytic squamous cell carcinoma of the vulva that mimics angiosarcoma on histology. We present a case of a 57-year-old woman with bilateral inguinal metastatic disease at the time of diagnosis, who died 4 months later because of distant metastatic disease to the lungs. Molecular analysis did not reveal any human papillomavirus infection. Because of the positive p53 immunostaining and the association to lichen sclerosus and simple type of high-grade vulvar intraepithelial neoplasia, alteration of p53 tumor suppressor gene might be involved in the pathogenesis of vulvar pseudoangiosarcomatous squamous cell carcinoma. However, further molecular studies are required.
 ...
PMID:Adenoid squamous carcinoma (pseudoangiosarcomatous carcinoma) of the vulva: a rare but highly aggressive variant of squamous cell carcinoma-report of a case and review of the literature. 1831 10


1 2 Next >>