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)

Aberrant p53 immunoreactivity has been found in skin pre-malignancies and dysplasias such as Bowen's disease and actinic keratoses. Vulval lichen sclerosus (LS) has been reported to be pre-malignant, with an association of vulval carcinoma in 3% to 6% of patients. In contrast, non-genital LS appears to have no malignant potential. In this immunocytochemical study, we investigated p53 expression in 10 cases of histologically proven vulval LS and 9 cases of non-genital LS using the murine monoclonal antibody Do-1 raised against recombinant human p53 which reacts with both wild-type and mutant p53. None of the vulval specimens had epithelial dysplasia or malignancy. Normal vulval (7 cases) and non-genital skin (5 cases) were used as tissue controls, respectively. The cell proliferation index was also studied using the MIB 1 monoclonal antibody which detects the cell-cycle associated Ki-67 antigen. The technique of microwave irradiation for antigen unmasking was employed on formalin-fixed and paraffin-embedded tissues. There was a significant increase in p53 immunoreactivity in vulval LS (32.13 +/- 15.11 epidermal cells per 100 basal cells) compared to normal vulval skin (7.52 +/- 5.04 epidermal cells per 100 basal cells) (p < 0.001), whereas the MIB 1 labelling index was lower in vulval LS (39.45 +/- 15.88 epidermal cells per 100 basal cells) than in normal controls (86.26 +/- 32.31 epidermal cells per 100 basal cells) (0.001 < p < 0.01). In contrast, there was no significant difference in p53 immunoreactivity or MIB 1 labelling index between non-genital LS and normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Altered p53 expression and epidermal cell proliferation is seen in vulval lichen sclerosus. 779 88

In this study, immunohistochemistry was used to investigate p53 and proliferating cell nuclear antigen (PCNA) expression in 40 cases of lichen sclerosus et atrophicus (LSA). Nuclear immunoreactivity for both p53 and PCNA was found in the basal and parabasal keratinocytes in the majority (91%) of the lesions. Typically, there was a widely varying positivity for PCNA, suggesting a wide range of proliferative capacity in individual LSA lesions. Lesions with p53 positivity in 5% or more of the basal cells also presented a strong (> 14% of basal cells positive) PCNA positivity (p = 0.030) and exhibited a higher mitotic rate (p = 0.002), suggesting a causal relationship between enhanced p53 expression and elevated cell proliferation. Lesions with a low number of PCNA-positive cells (< 15% of basal and parabasal cells positive) exhibited a wider subepithelial edematous zone and a thinner epithelium than in the lesions with a higher number of PCNA-positive cells. The results show that later stages of LSA, typified by subepithelial edema and epithelial atrophy, are associated with decreased proliferative activity of the basal and parabasal cells.
 ...
PMID:Expression of p53 and proliferating cell nuclear antigen in lichen sclerosus et atrophicus with different histological features. 792 51

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 histological changes of lichen sclerosus (LS) are frequently found in association with vulvar squamous cell carcinoma (SCC). The importance of chronic inflammation and scarring in oncogenesis is well recognized. Thirty-two patients with symptomatic vulvar LS and 60 with vulvar SCC were studied. Paraffin sections of vulvar LS, and three controls groups (acute scars, normal vulva, and vulvar lichen simplex chronicus [LSC]) were investigated with a panel of seven tissue markers and for DNA content in areas without vulvar intraepithelial neoplasia (VIN). All published cases to date of vulvar LS associated with SCC were reviewed. Of the cohort of symptomatic vulvar LS patients (mean/median age, 60 years), 9% developed VIN lesions and 21% invasive SCC; symptomatic LS preceded the carcinoma by a mean of 4 years (range, 1 to 23 years). Second and third primary tumors developed in three of these patients. Of the series of 60 patients presenting with vulvar SCCa, the clinical setting and histological features of SCCs associated with LS were significantly distinctive compared with SCCas without LS: SCCs associated with LS occurred in an older age-group (74 v 65 years; P = .01), were located on the clitoris (41% v 5%; P = .003), were of conventional SCCa type (85% v 57%; P = .02), were associated with a prominent fibromyxoid stromal response (46% v 10%; P = .004), were not associated with VIN 3 (SCC in situ) (5% v 67%; P = .02) and diffusely expressed tumor suppressor gene product p53 (43% v 19%; P = .01) and cytokine TGF-beta (33% v 9%; P = .05). The epidermis of vulvar LS was similar to that of acute scars and differed significantly compared with normal vulva with respect to keratinocytic expression of markers to keratin AE 1, involucrin and filaggrin, epidermal thickness (0.13 mm [LS] v 0.05 mm [normal]; P < .03), and proliferative index by PCNA and Mib-1 labeling (53/60 [LS] v 15/19 [normal] per 200 basal cells [bc]; P < .003). Vulvar LS showed significantly higher expression of p53 than all three control groups (80 [LS] v 3 [normal]/44 [acute scar]/28 [LSC] per 200 bc; P < .008), and aneuploidy (33% v diploid controls) in the absence of VIN. Comparing LS with and without associated SCCa found significant increases in age of patients (74 v 66 years; P = .001), and DNA aneuploidy (52% v 11%; P = .0001) and no differences in epidermal thickness, sclerotic thickness, proliferative index, or p53 expression. However, those cases of LS with an aneuploid DNA content showed significantly elevated p53 expression (88 v 60/200 bc; P = .01) and epidermal thickness (0.16 v 0.11 mm; P = .005) compared with LS with a diploid DNA content. Review of published cases supports an association between LS and vulvar SCC. The phenomenon of chronic inflammation and scarring giving rise to carcinoma has been well documented. Vulvar lichen sclerosus (LS) is an inflammatory dermatosis characterized by clinicopathologic persistence and hypocellular fibrosis (sclerosis). A subset of vulvar SCCs is significantly associated with the presence of LS and diffusely express the p53 gene product. Keratinocytes affected by LS show a proliferative phenotype and can exhibit markers of neoplastic progression such as increased p53 expression and DNA aneuploidy. As a chronic scarring inflammatory dermatosis, vulvar LS could act as both "initiator and promoter" of carcinogenesis, explaining the frequent coexistence of these diseases. Because keratinocytes of LS significantly express tumor suppressor gene p53 protein, the p53 gene may be involved early in this proposed pathway of carcinogenesis.
 ...
PMID:Vulvar lichen sclerosus and squamous cell carcinoma: a cohort, case control, and investigational study with historical perspective; implications for chronic inflammation and sclerosis in the development of neoplasia. 974 9

The simplex (differentiated) variant of vulvar intraepithelial neoplasia (VIN) has not been well characterized. The authors studied the clinicopathologic features of 12 cases of simplex VIN and obtained follow-up data to assess its relationship to vulvar invasive squamous cell carcinoma (InvSCC). Expression of p53 protein was analyzed immunohistochemically and compared with adjacent non-neoplastic epidermal lesions. Assessment of human papilloma virus (HPV) deoxyribonucleic acid was done by polymerase chain reaction amplification and in situ hybridization. All patients were of postmenopausal age (mean age, 66.8 years). Three patients had a history of prior vulvar InvSCC and one had a separate synchronous vulvar InvSCC. Squamous hyperplasia was present in the adjacent epidermis in 10 patients and lichen sclerosus (LS) was present in four patients. Histologically, simplex VIN differed from "classic" VIN by its highly differentiated features. The characteristic features included parakeratosis, thickened epidermis with elongated and anastomosing rete ridges, enlarged abnormal keratinocytes with premature eosinophilic cytoplasmic differentiation extending deeply within the epidermis, whorling of enlarged keratinocytes or keratin pearl formation within rete ridges, prominent intercellular bridges, and dysplastic basilar cells. One patient had minimal microinvasion (0.6 mm). Ten of 12 patients had positive p53 immunostaining staining with suprabasilar extension of p53 positive cells in each patient. The labeling index (LI) of basilar cells ranged from 0% to 99% (median, 94.5%). Non-neoplastic lesions in the adjacent epidermis had p53-positive basal cells in nine of 11 evaluable cases. The LI was significantly lower in these lesions, with a median of 4% in squamous hyperplasia and 7.5% in LS; none had suprabasilar extension of p53-positive cells. HPV (type 31/35/51) was identified in only one simplex VIN--a p53-negative lesion. Staining for p53 often delineated sharply the junction between simplex VIN and squamous hyperplasia. Four patients subsequently developed vulvar InvSCC at 5, 6, 9, and 55 months. All four InvSCCs were of the conventional keratinizing type and were HPV negative, as were the one synchronous and two prior InvSCCs. The authors conclude that (1) simplex VIN has a strong association with vulvar InvSCC and is a probable precursor lesion of HPV-negative vulvar InvSCCs, (2) HPV is very uncommon in simplex VIN and probably does not play an important role in its genesis, (3) alteration of the p53 gene appears to be involved in the development of simplex VIN, and (4) immunostaining for p53 protein may be helpful in the differential diagnosis of simplex VIN.
 ...
PMID:Vulvar intraepithelial neoplasia of the simplex (differentiated) type: a clinicopathologic study including analysis of HPV and p53 expression. 1071 58

A novel cell line, named LSA, has been obtained, stabilized, and characterized from a human liposarcoma. These cells have morphological and biochemical features strongly resembling the adipocytes and were able to grow in the Ham's F12 medium, in presence or absence of FCS. A conditioned medium (LSA-CM) was obtained by growing the LSA cells in the F12 medium in the absence of FCS. LSA-CM had cytostatic and cytotoxic effects (apoptosis and necrosis) associated with down-regulation of c-myc and upregulation of p53 in several human cell lines (breast, lung, glioblastoma, etc. ). The MCF-7 and glioblastoma cells were killed by LSA-CM in 5-6 days, whereas the same cells were killed by LSA-CM co-incubated with low doses of cisplatin in 30 h. LSA-CM peri-tumoral injections for 15 days in Balb-c-fc3H mice affected by mammary tumors, resulted in the rapid disruption of tumors and absence of metastases. In contrast, in the untreated animals the tumor masses were 4 times larger than initial lesions, and numerous metastases were found in the lungs. The toxicity analysis of LSA-CM, performed on three different animal species, showed that LSA-CM is absolutely free of acute, subacute, and subchronic toxicity. The possible use of LSA-CM/cisplatin for cancer treatment is discussed.
 ...
PMID:A conditioned medium from a human liposarcoma-derived cell line induces p53-dependent apoptosis in several tumor cell lines. 1076 81

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

To determine if carcinogenic events in vulvar skin precede the onset of morphologic atypia, the authors investigated for derangements in DNA content, cell proliferation, and cell death in vulvar carcinomas and surrounding skin in 140 samples of tumor and surrounding skin collected from 35 consecutive vulvectomy specimen for squamous cell carcinoma (SCC) or vulvar intraepithelial neoplasia (VIN) 3. Vulvar non-cancer excisions were used as controls. Investigations consisted of histologic classification and measurement of 9 variables--epidermal thickness (acanthosis and rete ridge length), immunolabeling index (LI) for 3 proteins (p53 protein, Ki-67, and mdm-2), pattern of p53 expression (dispersed vs. compact), DNA content index, and presence of aneuploidy by image analysis and apoptotic rate by Apotag labeling. Significant positive correlations were found for all nine variables studied versus increasing histologic severity in two proposed histologic stepwise models of vulvar carcinogenesis (lichen sclerosus (LS) and VIN 3 undifferentiated associated SCC groups). High p53 LI (>25) and the compact pattern of p53 expression (suspected oncoprotein) significantly correlated with LS and its associated vulvar samples compared with samples not associated with LS (P < or = 0.001). Furthermore, p53 LI, mdm-2 LI, and pattern of p53 expression were concordant between patient matched samples of LS and SCC. In addition, mdm-2 LI significantly correlated with dispersed pattern p53 LI suggesting a response to wild-type p53 protein accumulation. These findings support the hypothesis that neoplastic transformation occurs in sequential steps and compromises proteins involved in the cell cycle control. Concordance of p53 and mdm-2 protein expression in LS and adjacent SCC provides evidence that LS can act as a precursor lesion in the absence of morphologic atypia. Overexpression of mdm-2 with stabilization and inactivation of p53 protein may provide an alternate pathway for vulvar carcinogenesis.
 ...
PMID:Concordant p53 and mdm-2 protein expression in vulvar squamous cell carcinoma and adjacent lichen sclerosus. 1139 33

We studied some of the morphological and immunohistochemical parameters of lichen sclerosus (LS) and carcinomas of the vulva in order to verify some characteristics in LS related to neoplasm transformation. Parameters such as proliferating index, rate of proliferation of lymphoid elements into a tumor and types of such elements were studied. In parallel, the number of cells positive to apoptosis-related proteins such as Fas, Fas ligand, p53 and bcl-2 were evaluated. Biopsy material from patients with different vulvar disorders--22 samples with LS and 23 samples with vulvar squamous cell carcinoma (VSCC)--was studied by the methods of morphometry and immunohistochemistry. In LS, the number of T cells is a few times higher than those of B cells. Among the T cells, the number of killers is significantly higher than the number of helpers. Carcinomas, especially those with lymphoid depletion, are characterized by a further significant increase in some parameters such as the rate of lymphoid proliferation and the number of T helpers and killers. The progression in to tumorigenesis was accompanied with a significant increase in the number of Fas+ and FasL+ lymphocytes. In tumor epithelial cells the proliferative index increased in carcinomas with lymphoid depletion. The number of p53+ epithelial cells increased whereas the number of bcl-2+ cells showed a distinct tendency to decrease with progression in to tumorigenesis. Development of a tumor is manifested in deep changes in relationships between different lymphoid components. Only two lymphoid markers are significantly different in VSCC compared to LS: the number of T killers and macrophages. The other parameters studied (rate of proliferative activity, the total number of T cells and T helpers, B cells, IL-2-connective cells) already showed high expression in LS as the first signs of transformation of this inflammation into neoplasia.
 ...
PMID:Lymphoid elements and apoptosis-related proteins (Fas, Fas ligand, p53 and bcl-2) in lichen sclerosus and carcinoma of the vulva. 1144 71

Seventy-one cases of invasive squamous cell carcinoma (ISCC) of the vulva were compared with 18 cases of vulvar intraepithelial neoplasia (VIN) and 21 cases of lichen sclerosus. Ploidy was studied by image analysis, HPV-DNA by PCR, and p53 and pRb by immunohistochemistry. Univariate and multivariate statistical analyses were performed. The mean age of the patients with ISCC was 70.6 years; only 8.5% were < 60 (range, 43-89) years. For the 43 patients with follow-up, FIGO surgical stages were I in 16.2%, II in 48.8%, III in 27.9%, and IV in 6.9%. The 5-year survival was 90% for the patients with curative surgery (vulvectomy and lymphadenectomy) and 32% for those with tumors in stages III to IV. Previous history of nonneoplastic epithelial alterations was recorded in 54%. Vascular invasion was detected in 4.3% and perineural invasion in 21.4%. Inguinal lymph node metastases were present in 34.9% of the cases. Fifty-one (72%) ISCCs were aneuploid, HPV-DNA-16 was detected in 7 (12.3%) cases, overexpression of p53 was found in 40 (56%), and pRb expression was negative in 15 (21.4%). Fifteen cases (80%) of VIN were aneuploid, 5 (27.7%) contained HPV-DNA, 11 (61%) were positive for p53, and all immunoreacted for pRb. All lichen sclerosus cases were diploid, did not contain HPV-DNA, failed to stain for p53, and were positive for pRb. Our study confirmed the prognostic value of conventional pathological features: stage, lymph node metastasis, histological grade, and vascular and perineural invasion; all were statistically significant for survival in the univariate analysis. Also, ploidy was significant in patients with stages I and II tumors. The only significant variable in the multivariate analysis was stage. p53 overexpression appears as a late event in vulvar carcinogenesis, but it may occur before tumor invasion. Lack of pRb expression can occur in vulvar neoplasia, but it does not seem to play any role in the initiation or prognosis of vulvar ISCC.
 ...
PMID:Squamous cell carcinoma of the vulva: study of ploidy, HPV, p53, and pRb. 1209 May 85


1 2 3 4 Next >>