الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 116 |  |  |
| | | from | 116 | | |
Abstract
Lichen planus is a pruritic dermatosis of unknown etiology that affects skin, oral and genital mucous membranes, nails and hair. Many factors were suggested to be involved in the etiology of LP, including HLA association, infectious agents, drugs, diabetes, hepatic diseases, GVHD and psychological factors, but none of these was proved, however it is believed to be an autoimmune process involving T cells directed against basal keratinocytes. Lichen planus is characterized histologically by subepithelial band-like inflammatory infiltrate associated with apoptosis of keratinocytes and breaks in the epithelial basement membrane that leads to basal cell liquefaction. Caspases are cysteine-proteases of the IL-1β-converting enzyme family, which are required for apoptosis. Many caspases participate in a cascade analogous to the coagulation system; upstream caspases cleave and activate downstream caspases, which in turn cleave the various substrate proteins which account for many of the biochemical and morphological changes that occur during apoptosis. Although all members of the caspase family share similarities in amino acid sequence and structure, they differ significantly in their physiologic roles. The caspases can be broadly divided into two groups: those that are centrally involved in apoptosis (caspase-2, -3, -6, -7, -8, -9, and -10) and those related to caspase-1 (caspase-1, -4, -5, -13, and -14, as well as murine caspase-11 and -12), whose primary role appears to be in cytokine processing during inflammatory responses. Amongst these proteases, caspase-3 (CPP32) is the most downstream enzyme in the apoptosis-inducing protease pathway and is probably the most clearly associated with cell death. After caspase-3 cleavage and activation, there is no return in the cell death pathway, since it cleaves key proteins in the cell repairing process. As apoptosis appears to be the mode of cell death by which damaged cells are removed from the lesional tissue in lichen planus, so we aimed by this study to evaluate the possible involvement of caspase-3 in the pathogenesis of LP. This study was conducted on 25 patients with different clinical varieties of LP; classic, hypertrophic, actinic and combined type. In addition to 17 apparently normal persons served as controls. They were from the Dermatology Out-Patient Clinic Menofia University Hospitals during the period from April 2010 to June 2012 while controls were collected from plastic surgery clinic. All participents were subjected to complete history taking, thorough general and dermatological examination, after informed written consent punch biopsies of 4 mm were taken after sterilization, under local anaesthesia from the LP skin, and the normal skin. Biopsies of both groups were prepared for routine haematoxylin and eosin (H&E) staining and immunohistochemical staining using mouse monoclonal anti caspase-3 antibody. The results of this study revealed the following: Patients and controls were age and sex matched (P> 0.05). The mean duration of the LP group was (1.85±4.02) years. According to the clinical types of LP patients, 72% showed classic LP, 12% showed hypertrophic LP, 12% showed actinic LP and 4% presented with combined type of classic & actinic LP. In controls caspase 3 expression was detected in keratinocytes of 5 cases (29.4%) only, with panepidermal pattern of distribution which was of mild intensity in 4 cases and moderate in one case. In LP cases caspase 3 expression in epidermal keratinocytes was positive in 18 cases (72%), with mild intensity in 8 cases, moderate in 7 cases and strong in 3 cases. Twelve cases (66.7%) showed only cytoplasmic expression with pan-epidermal pattern while six cases (33.3%) showed both cytoplasmic and nuclear expression of basal and parabasal distribution. High significant elevation in caspase 3 expression was present in LP cases (72%) compared to control subjects (29%) (P> 0.05). No significant association between caspase-3 expression or intensity of epidermal keratinocytes in LP cases and any of the studied clinicopathological parameters. However Statistically significant association was found between patterns of distribution of caspase 3 expression in keratinocytes and site of LP lesions as well as hypergranulosis. Dermal inflammatory infilterate showed positive expression of caspase 3 in 21 cases (84%), that was of mild intensity in 4 cases, moderate in 16 cases and strong in one case. Six cases showed focal distribution of caspase 3 expression and the other 15 cases revealed diffuse distribution. No statistically significant association was present between caspase 3 expression or intensity in dermal lymphocytic inflammatory infilterate and any of studied clinicopathological parameters except age of patients as young age group showed strong intensity while older one showed mild expression. Regarding the pattern of caspase 3 expression in dermal lymphocytes no significant relationship of distribution of caspase 3 expression in dermal lymphocytes with the studied clinicopathological parameters except with associated HCV infection. No significant correlation was found between caspase 3 expression in epidermal keratinocytes and dermal lymphocytic inflammatory infilterate in LP cases.