CD93 has a crucial role in pathogenesis of psoriasis.

BACKGROUND: Psoriasis is a chronic, immune-related disorder; inflammation, higher rate of epidermal proliferation, and angiogenesis are the main pathognomonic features. Cluster of differentiation 93 (CD93), an angiogenic element, plays a role in cell adhesion regulation and has a putative function in inflammation. OBJECTIVE: To assess CD93 immunohistochemical expression in psoriatic skin and the association of CD93 single nucleotide polymorphisms (SNPs) rs2749817 to disease pathogenesis and severity. METHODS: This case-control study was done on 50 patients with psoriasis vulgaris beside 50 age- and sex-matched healthy controls. Assessment of psoriasis severity was done by Psoriasis Area and Severity Index (PASI) score. 3 mm punch skin biopsies were taken from every participant, and hematoxylin and eosin staining and immunohistochemical staining for CD93 antibody were done. Assessment of CD93 rs2749817 gene polymorphism by the TaqMan allelic discrimination assay technique (real-time PCR) was done. RESULTS: Immunohistochemical expression of CD93 showed membrano-cytoplasmic localization in both endothelial and inflammatory cells of cases and controls with significant more positivity in dermal endothelial and inflammatory cells of cases than controls (p = 0.001 and 0.014 respectively). Strong intensity was present in 18 of cases endothelial cells and 24 inflammatory cells with absence in controls (p =  0.001 for both) with significantly higher H-score and higher percent of positive cells (p  =  0.001 for both). The TC genotype was lower in patients compared to control (p-value = 0.006) and CC genotype which was present only in cases (p-value = 0.021). CONCLUSION: Cluster of differentiation 93 has an essential role in psoriasis and an encouraging future therapy for psoriasis.

Role of CYR61 in psoriatic lesional and perilesional skin: A clinical and immunohistochemical study.

BACKGROUND: Psoriasis is considered as an immune-mediated disorder with significant epidermal hyperplasia and inflammation. Cysteine-rich angiogenic inducer 61 (CYR61), known as CCN family member 1 (CCN1), plays an important role in cell proliferation and neovascularization which may trigger psoriasis development. AIMS: This study aimed to assess the immunostaining of CYR61 in psoriatic skin (lesional and perilesional) compared to control skin. PATIENTS/METHODS: This is a case-control study. The Psoriasis Area and Severity Index (PASI) was used to evaluate disease severity. A punch biopsy was taken from psoriatic skin lesions (30), perilesional (30) skin, and matched site of controls (20). The pathological and immunostaining assessments of CYR61 were conducted. RESULTS: There was a significant gradual progressive overexpression of CYR61 in keratinocytes from control skin to perilesional and lesional psoriatic skin (P = .00). Moreover, lesional psoriatic skin showed overexpression of CYR61 in inflammatory cells in the dermis than controls. CYR61 expression (lesional epidermis) revealed a significant positive correlation with the PASI score (r = .63; P = .00). There was a significant relationship between intensity and H-core of CYR61 in the lesional psoriatic epidermis with joint affection. CONCLUSION: CYR61 may trigger epidermal hyperplasia and potentiate inflammatory infiltration in psoriasis vulgaris patients, and therapies targeting CYR61 may be effective in the management of psoriasis vulgaris.

Tissue expression of IL-17A and FOXP3 in acne vulgaris patients.

BACKGROUND/OBJECTIVES: CD4+  T helper (Th) cells through its pro-inflammatory cell type, interleukin-17 (IL-17)-generating cells and its anti-inflammatory category forkhead box P3-positive (FOXP3+ ) regulatory T (Treg) cells, play a vital role in the immune balance in inflammatory disorders. Therefore, assessment of both IL-17 and FOXP3 in acne vulgaris (AV), a chronic inflammatory disease of the pilosebaceous unit, could be of value in understanding AV pathogenesis. This study aimed to investigate the immunohistochemical expression of IL-17A and FOXP3 in acne vulgaris lesions versus normal skin. METHODS: Forty-five AV patients and 25 controls were included in this case-control study. Biopsies from participants were analyzed for IL-17A and FOXP3 immunohistochemical profiles using IL-17A and FOXP3 polyclonal antibodies. RESULTS: Compared to controls, AV patients exhibited a significant increase of IL-17A percent of expression in epidermis (P ≤ .001), in lymphocytes in papillary dermis (P ≤ .001), and in perifollicular lymphocytic inflammatory infiltrate in AV lesions. Also, there was a significant elevation in FOXP3 percent of expression in epidermis (P = .049) and in lymphocytes in papillary dermis (P ≤ .027) in acne patients than control. A significant positive correlation between IL-17A expression in papillary lymphocytes and in epidermal keratinocyte was observed (r = .537, P = .001). In acne vulgaris patients, the associations between IL-17A and FOXP3 expressions could not reach level of significance. CONCLUSIONS: There was an up-regulation of IL-17A and FOXP3 in acne vulgaris development, but with independent roles. Moreover, targeting of IL-17A and FOXP3 may open the door for development of new therapeutic agents in acne vulgaris treatment.

Role of mast cells in skin tag development: an immunohistochemical study.

OBJECTIVE: To detect mast cell density by toluidine blue and immunohistochemical staining for mast cell tryptase in skin tags as compared to normal skin to determine whether they have a role in skin tag development. STUDY DESIGN: This study was carried out on 30 patients with skin tags and 10 age- and sex-matched healthy controls without skin tags. RESULTS: There was a significant difference between skin tag and control groups regarding mast cell density evaluated by toluidine blue staining (p = 0.003) and mast cell tryptase expression (p = 0.001), where the density was higher in skin tags as compared to normal skin. Mast cells were higher in number using toluidine blue staining in lesions arising in sites other than the head and neck (p = 0.028). High expression of mast cell tryptase was significantly associated with marked collagenosis (p = 0.02) and presence of eosinophils (p = 0.04). CONCLUSION: The present study demonstrates the possible role of mast cells in promoting fibrosis and facilitating the development of skin tags. Mast cells may attract eosinophils to cooperate in inducing more fibrosis in skin tag development.

Immunohistochemical expression of perforin in lichen planus lesions.

BACKGROUND: Lichen planus (LP) is a chronic inflammatory papulosquamous skin disease characterized by epidermal basal cell damage and a particular band-like infiltrate predominantly of T cells in the upper dermis. It is characterized by the formation of colloid bodies representing apoptotic keratinocytes. The apoptotic process mediated by CD8+ cytotoxic T lymphocytes and natural killer cells mainly involves two distinct pathways: the perforin/granzyme pathway and the Fas/FasL pathway. So far, little is known regarding the role of perforin-mediated apoptosis in LP. AIM: Is to study the expression and distribution of perforin in the epidermis and dermis of lesional LP skin. MATERIALS AND METHODS: Skin biopsy specimens from lesional skin of 31 patients with LP and 10 healthy persons were analyzed by immunohistochemistry. RESULTS: Significant accumulation of perforin + cells was found in both epidermis and dermis of LP lesions compared with healthy skin. Perforin expression was significantly upregulated in the epidermis of LP lesions. CONCLUSION: Accumulation of perforin + cells in the epidermis of LP lesions suggest a potential role of perforin in the apoptosis of basal keratinocytes.

Immunohistochemical expression of heat shock protein 70 in vitiligo.

Heat shock proteins (HSPs) are proteins that are expressed under variety of stresses including pathologic conditions. How stresses affect vitiligo is not fully understood and little is known about the role of HSPs generally and Hsp70 specifically in vitiligo. The current study investigated the expression of Hsp70 in vitiliginous (32) and normal skin (10) by immunohistochemistry together with correlating this expression with the clinicopathologic parameters in the studied vitiligo group. Hsp70 was expressed in the cytoplasm of epidermis in all normal skin compared with its localization to the cytoplasm in 35.5% and to the nuclei in 64.5% of epidermis in vitiligo lesions. Intense (P < .001) and diffuse (P < .001) expression of Hsp70 was in favor of vitiligo skin compared with normal skin. Nuclear form of Hsp70 tended to be expressed in progressive forms of the disease. The percentage of Hsp70 expression tended to be decreased with the duration of the disease. From the present study, up-regulation of HSP 70, in the form of its intense and diffuse expression, may be blamed in pathogenesis of vitiligo. Nuclear localization of HSP 70 may be more important than its presence or absence, beside it may be related to progression of the disease.

Immunolocalization of tenascin-C in vitiligo.

The disappearance of melanocytes because of defective adhesion is one of the accepted theories to explain vitiligo. Tenascin-C is a large, extracellular matrix glycoprotein that is thought to inhibit adhesion of melanocytes to fibronectin. The current study aimed to evaluate the pattern of tenascin-C expression in vitiligenous skin compared with normal pigmented skin by means of immunohistochemistry. The study was carried out on skin biopsies from lesional and perilesional skin of 30 patients with vitiligo and on normal skin of 10 healthy volunteers. Several histopathologic changes were observed in vitiliginous skin such as keratinocyte vacuolization, a thickened basement membrane, and dermal inflammatory changes. Tenascin-C was expressed in keratinocytes of the basal epidermal layer of normal skin biopsies at a mild intensity but it did not stain the dermis, whereas vitiligenous skin showed tenascin-C expression in most cases (93.3% ), in the papillary dermis, epidermis, and in both. Diffuse epidermal expression of tenascin-C correlated with more loss of pigment and continuous staining of tenascin-C in the papillary dermis correlated with progressive forms of vitiligo. Intense tenascin-C expression was associated with a more progressive course of the disease assessed by the vitiligo disease activity score. From this study, tenascin-C is highly expressed in the dermis, epidermis, and both of vitiligo as a secondary event for the disease. Keratinocyte is a source of tenascin-C in vitiligo, and diffuse epidermal expression of tenascin-C may induce more loss of melanocytes and melanin pigment. Dermal expression of tenascin-C in the vitiligenous lesion may be linked to the disease more than epidermal expression, because this pattern is only seen in a vitiligenous lesion and it is completely absent in normal and perilesional skin.

Up-regulation of Notch-1 in psoriasis: an immunohistochemical study.

The Notch pathway plays a key role in differentiation, proliferation, and influencing cell fate decision in multiple organisms and tissues including the epidermis and its appendages. The role of Notch-1 in psoriasis has not been widely evaluated; therefore, the current study aimed to evaluate its role in etiopathogenesis of this common skin disease. The current study used immunohistochemical technique to evaluate Notch-1 expression in 35 lesional biopsies of patients having chronic plaque psoriasis in comparison with normal skin biopsies, representing the control group. Notch-1 was expressed in the epidermis of both normal and psoriatic skins; however, the intensity was in favor of psoriatic lesion, and the nuclear form of Notch-1 was more frequently and diffusely seen in psoriasis. Exacerbation of psoriasis as assessed by the Psoriasis Area and Severity Index score was significantly associated with intense (P = .005) and nuclear form of Notch-1 expression (P = .0001). The nuclear form of Notch-1 was also correlated with female sex (P = .043). From this study, up-regulation and not down-regulation of Notch-1 may have a role in pathogenesis of psoriasis. The nuclear form is responsible for the exacerbation of symptoms, and it is the one that may disappear by the effect of psoralen and ultraviolet A radiation (PUVA) therapy.

Maspin expression in epithelial skin tumours: an immunohistochemical study.

BACKGROUND: Maspin is a member of the serpin family of protease inhibitors and is thought to inhibit carcinoma invasion, metastasis, angiogenesis and induce apoptosis. AIM: The aim of this work is to investigate maspin expression in cutaneous basal and squamous cell carcinomas by means of immunohistochemistry. MATERIALS AND METHODS: This study was carried out on 43 patients, 25 basal cell carcinoma (BCC) and 18 squamous cell carcinoma (SCC) together with ten apparently healthy volunteers as a control group. RESULTS: There was a significant difference between the malignant and control groups regarding maspin expression since all control cases showed maspin expression compared to 60.5% (26/43) positivity in malignant cases. Maspin positive expression tended to be of higher percentage in SCC (77.8%) compared to BCC (48%) (P = 0.06) and the strong intensity of maspin was also significantly in favour of SCC compared to BCC (P = 0.02). The staining of both the cytoplasm and nuclei was seen in 27.7% of SCC and 12% of BCC and was significantly in favour of older age group (P = 0.02) and the adenoid variant (P = 0.04) of the latter. CONCLUSIONS: Maspin is associated with terminal squamous differentiation. Nuclear staining of maspin is seen in both BCC and SCC with a suggested tumour suppressor role in BCC.

Cathepsin D expression in chronic plaque psoriasis: an immunohistochemical study.

Cathepsins are lysosomal cysteine proteases, which are involved in a variety of physiologic processes such as proenzyme activation, antigen presentation, tissue remodeling, bone matrix resorption, and pathologic processes such as facilitating tumor invasion and modulating the process of programmed cell death. This study aimed to evaluate the pattern of cathepsin D (CD) expression in chronic plaque psoriasis in comparison to normal skin by means of immunohistochemistry. The study included 34 patients presenting with chronic plaque psoriasis and 10 age- and sex-matched normal subjects as control group. Sixty percent of normal skin showed granular positivity for CD confined to basal layer. CD is upregulated in psoaritic lesion with 94.1% positivity making a significant difference between psoriasis and normal skin as regards the percentage and distribution of CD expression, where the latter was predominantly diffuse in psoriatic lesion. The eight cases exposed to PUVA therapy showed reduction of CD positivity to 62.5% with a predominance of mild staining and focal expression compared to pretreatment biopsies. CD may have a role in the pathogenesis of psoriasis in view of its high percentage and diffuse expression in psoriatic epidermis. CD degradative capacity may be responsible for disordered differentiation and scale formation characteristic of psoriasis. Reduction of CD expression may be one of the pathways of PUVA mechanism of action.

Immunohistochemical expression of ezrin in cutaneous basal and squamous cell carcinomas.

Ezrin is a member of the ezrin-radixin-moesin family of proteins, which link the actin-containing cytoskeleton to the plasma membrane. Overexpression of ezrin protein is correlated with the metastatic potential in several cancers. Little is known about the distribution of ezrin in normal epidermis and nonmelanoma skin cancer; therefore, in the current study, we examined the immunohistochemical expression of ezrin in normal skin (10 biopsies) and epithelial skin tumors (25 basal cell carcinoma [BCC] and 20 squamous cell carcinoma [SCC]). Ezrin was expressed in epidermis of all normal controls with a prominent membranous pattern compared with 93.3% positivity in malignant cases with a significant higher intensity (assessed by H score) in favor of the latter (P = .002). Cytoplasmic expression of ezrin either alone or associated with membranous expression was both seen in BCC and SCC. The median value of H score in SCC (160) cases was higher than that in BCC (60). H score values of ezrin expression in BCC was significantly higher in tumors arising in sites other than the head and neck (P = .04). In SCC, the intensity of ezrin expression tended to be associated with advanced stage (P = .08). Our study demonstrated the probable tumorigenic role of ezrin in epithelial skin tumor formation. It may enhance local invasion or metastasis of epithelial skin tumors, which necessitates further larger study to clarify. The intensity rather than the pattern of ezrin expression had a more probable impact on the tumor behavior.

Immunohistochemical expression of TGF-ß1 in keloids and hypertrophic scars.

BACKGROUND: Aberrant wound healing of skin injury may lead to 2 pathologic entities, termed keloids and hypertrophic scars (HS). There has been growing evidence suggesting a role for transforming growth factor beta (TGF-ß) family members in the pathogenesis of fibrosis. OBJECTIVE: The aim of the present work was to investigate the role of TGF-ß1 in the pathogenesis of keloids and HS. MATERIAL AND METHODS: TGF-ß1 was analyzed on skin biopsies of 30 patients presenting with keloids (16) or HS (14) and 10 normal surgical scar and 10 age- and sex-matched normal subjects (controls). RESULTS: TGF-ß1 was expressed in dermal fibroblasts, inflammatory cells, and endothelial cells of normal surgical scar (60%) and aberrant scar (86.7%) with an absence of statistical difference. Although it is expressed in 90% of epidermis of aberrant scar (diffuse expression) compared with 60% of normal surgical scar (basal layer expression) and 20% of normal skin biopsies (basal layer expression) with highly significant differences. Dermal TGF-ß1 expression in aberrant scar lesions was significantly associated with lesions of shorter duration (P = 0.01) and older age group (P = 0.02). The intense dermal expression was also associated with lesions of shorter duration (P = 0.0001) and immature scars (P = 0.002). CONCLUSIONS: TGF-ß1 is involved in the pathogenesis of both keloids and HS with maximum effect at early stages. Keratinocytes are not passive partners but rather may have an active role in the induction of fibrosis. Targeting of TGF-ß1 may be of benefit if applied early and if directed against keratinocytes as an unusual target of therapy.