الفهرس 
- THE CELL CYCLEOnly 14 pages are availabe for public view
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Abstract
Psoriasis is a chronic relapsing skin disease characterized by sharply demarcated scaly erythematous plaques. It varies in severity from minor localized plaques to complete body coverage and sometimes is associated with psoriatic arthritis.
It affects both sexes equally and can occur at any age, although it most commonly appears for the first time between the ages of 15 and 25 years. The disease may be provoked in genetically predisposed individuals by a number of precipitating factors including stress, alcohol consumption, drugs, sunlight, skin trauma, infections and hormonal factors.
Psoriasis represents a T-cell- mediated inflammatory skin disease. Although the primary pathogenic mechanism is still unknown, several cytokines form a complex and multi-dimensional network in the pathogenesis of psoriasis. However, none of which alone can be considered to be the causative mechanism. P53 protein is a protein encoded for by P53 gene present on the short arm of chromosome 17. It is composed of 393 amino acids roughly organized into 3 regions or domains.
P53 in its natural form or wild type plays an important role in regulation of cellular proliferation. It inhibits cell cycle progression and cell growth by down-modulating, directly or indirectly, the expression of genes that are required for ongoing cell proliferation. It also arrests the cells in G1 phase of the cell cycle, after DNA damage, allowing repair of breaks in the DNA strands thus reducing the probability of mutations. If the DNA damage is extensive P53 triggers programmed cell death or apoptosis.
Wild type P53 have a short half life while mutant P53 have longer half life. That’s why mutant P53 can be easily detected by immunohistochemical methods in contrast to wild type P53.
Mutant P53 gene has the ability to transform cells and lead to tumor formation. Mutation of P53 gene are the most frequent genetic alteration in human malignancies but there is marked controversy about its role in benign hyperproliferative skin disorders.
P53 protein has the ability to interact with several viral and cellular proteins as large T-antigen of simian virus 40, the E1B protein of adenovirus, the E6 protein of HPV, and the cellular protein MDM2.
The aim of this study was to identify the expression of P53 in psoriatic patients with different clinical types and severity to clarify its role in the pathogenesis of psoriasis and its correlation with the disease severity.
This study included; 30 patients of different clinical variants of psoriasis and 25 controls. All patients were subjected to complete history taking, clinical examination including psoriasis area and severity index (PASI) score and skin biopsies, all patients stopped topical or systemic medication 4 weeks prior to biopsies.
Five mm incisional biopsy specimens were taken from the 30 patients. The specimens were placed in 10% neutral buffered formalin to be paraffin embedded. Two slides were made from each biopsy, one stained with hematoxylin and eosin to confirm the diagnosis while the other was cut on positive charged adhesive slide to be prepared for immunohistochemical detection using mouse monoclonal antibody (Do7) against P53 protein. Results were compared with 25 control normal skin biopsies.
The patients group consisted of 16 males (53.3%) and 14 females (46.6%). Their age ranged between 18 to 60 years with mean + SD (36.3 + 9.7).P53 nuclear staining was detected in 13 out of the 30 patients (43.3%), while the other 17 (56.7%) showed negative immunoreactivity either nuclear or cytoplasmic.
The patients were divided into six subgroups according to the clinical types of psoriasis. Five patients (16.6%) with psoriasis vulgaris, 2 of which (40%) show negative intensity of staining of P53 expression and 3 of which (60%) show mild P53 expression. Five patients (16.6%) with guttate psoriaseis all of them (100%) show negative P53 expression. Five patients (16.6%) with psoriasis of palm and sole, 1 of which (20%) shows negative P53 expression and 4 of which (80%) show mild P53 expression. Five patients (16.6%) with Nail psoriasis, 4 of which (80%) show negative P53 expression and 1 of which (20%) shows mild P53 expression. Five patients (16.6%) with flexural psoriasis all of them show negative P53 expression. Five patients (16.6%) with erythrodermic psoriasis; 2 of which (40%) show mild P53 expression and 1 patient (20%) shows moderate P53 expression and 2 patients (40%) show strong P53 expression.
The PASI score of the patients ranged from 3.3 to 67.6 with mean + S.D (22.6+ 22.2). Three of the 30 patients (10%) had positive family history. Two out of the 13 patient with P53 expression had + ve family history.
The expression ranged from mild (10 cases, 76.9%) to moderate (1 case, 7.8%), to strong expression (2 cases, 15.4%).The 25 control group all showed negative P53 expression.
The statistically significant increase in P53 intensity with the clinical severity of psoriasis may raise the suspicion that P53 may have a role in determining disease severity and so we argued that P53 is an important marker of active cell cycling in psoriasis.