Alaa Hassan Maraee

Immunohistochemical Expression of TGF-β1 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-β) family members in the pathogenesis of fibrosis. Objective:The aim of the present work was to investigate the role of TGF-β1 in the pathogenesis of keloids and HS. Material and methods:TGF-β1 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-β1 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-β1 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-β1 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-β1 may be of benefit if applied early and if directed against keratinocytes as an unusual target of therapy.

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.

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.

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 GLUT-1 and Ki-67 in chronic plaque psoriasis.

Abstract:Many inflammatory mediators and other biological markers are upregulated in psoriatic lesions; some of these alterations also persist in nonlesional skin. Glucose is the major source of energy for cells, and glucose transporter 1 is the most common glucose transporter in humans (GLUT-1). The present study aimed at evaluating the pattern of expression of GLUT-1 and Ki-67 in psoriatic skin (involved and uninvolved) and correlating their expression with the clinicopathological parameters in the studied patients. This study was carried out on 30 patients presented with chronic plaque psoriasis and 10 apparently healthy volunteers as a control group. GLUT-1 was not expressed in epidermis of normal skin, whereas it was expressed in 76.6% of uninvolved and 86.7% of involved skin of psoriatic patients, where both the latter differed significantly regarding the intensity (P = 0.001) and localization (P = 0.001) of GLUT-1 expression. The percentage of Ki-67 expression did not differ significantly between involved and uninvolved skin of psoriatic patients, but they were higher than that of normal skin of control group. Nucleolar pattern of Ki-67 expression was significantly associated with male sex (P = 0.05), marked parakeratosis (P = 0.01), and marked angiogenesis (P = 0.05). GLUT-1 expression was associated with degree of acanthosis and percentage of Ki-67 expression. From this study, GLUT-1 is upregulated in psoriatic epidermis and may be involved in facilitation of keratinocyte proliferation in psoriasis. Nucleolar pattern of Ki-67 is an indicator of progressive keratinocyte proliferation in psoriasis.

Immunohistochemical evaluation of COX-1 and COX-2 expression in keloid and hypertrophic scar.

Abstract:Both keloids (KLs) and hypertrophic scars (HSs) are considered as dermal fibroproliferative diseases that differ clinically and histopathologically. Although several factors have been postulated in the etiopathogenesis of these conditions, there has been growing evidence to suggest the role of COXs in the pathogenesis of abnormal wound healing because of the reduction of formation of KL and HS in patients using nonsteroidal anti-inflammatory drugs and a COX-2 inhibitor. The aim of the present work is to evaluate the pattern and localization of COX-1 and COX-2 expression in KL and HS compared with surgical scars. COX-1 and COX-2 were analyzed on skin biopsies of 30 patients who presented with KL (15) and HS (15) and 10 normal surgical scars (controls). Both COX-1 and COX-2 were expressed not only in dermal components (fibroblasts, inflammatory cells, and endothelial cells) but also in keratinocytes of the overlying epidermis in the different studied scar lesions. The percentage of COX-1 expression increased progressively from surgical scar (40%) to HS (53.3%) to KL (100%) with a statistically significant difference (P = 0.002). COX-2 was expressed in 100% of surgical scars, 73.3% of HS and 86.7% of KL with the absence of significant differences (P > 0.05). The significant difference in COX-1 expression between HS and KL may refer to the presence of different pathways for the emergence of these diseases. The expression of COX-2 in all scars (normal or abnormal) indicates its active role as an inflammatory mediator. Keratinocytes play an active role in induction of scarring by up-regulation of inflammatory mediators, such as COX-1 and COX-2.

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.

Immunohistochemistry of Janus Kinase 1 (JAK1) Expression in Vitiligo.

Background Vitiligo is a chronic autoimmune disease in which the destruction of melanocytes causes white spots on the affected skin. Janus kinase (JAK) is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK–signal transducer and activator of transcription pathway. The aim of the present study is to explore the possible role of JAK1 in the pathogenesis of vitiligo using immunohistochemical methods. Methods The current study was conducted in a sample of 39 patients who presented with vitiligo and 22 healthy individuals who were age and sex matched as a control group. We used immunohistochemistry to evaluate JAK1 status (intensity and distribution) and assess the percentage of residual melanocytes using human melanoma black 45 (HMB45). Results Intense and diffuse JAK1 expression was significantly more likely to indicate vitiliginous skin compared to normal skin (p < .001). Strong and diffuse JAK1 expression was associated with short disease duration, female sex, and lower percentage of melanocytes (detected by HMB45) (p < .05). Conclusions JAK1 may be involved in the pathogenesis of vitiligo, as indicated by intense and diffuse expression compared to control and association with lower percentage of melanocytes detected by HMB45 immunostaining.

Tenascin-C expression in lichen planus

Objectives The aims of this study were to evaluate the immunohistochemical expression of tenascin-C (TN-C) in lichen planus (LP) and to highlight its hypothesized role in the etiopathogenesis of this disease entity. Background LP is an inflammatory disease of the skin and the mucous membrane, the exact etiology of which is not known; however, multiple theories have been proposed. TN-C is an extracellular matrix glycoprotein that plays different roles, mediating both inflammatory and fibrotic processes. However, little information about its role in LP exists. Patients and methods Thirty patients with LP and 10 age-matched and sex-matched volunteers as controls were included. They were subjected to complete history taking, and general and dermatological examination. Skin biopsies were taken from the lesional skin of LP patients and the normal skin of controls. Biopsies were subjected to routine hematoxylin and eosin staining and immunostaining for TN-C. Results Forty-three percent of LP cases showed epidermal expression, whereas most of the cases (77%) showed a positive dermal expression. Dermal expression of TN-C is significantly elevated in cases than in controls (P = 0.01). Positive correlations between the dermal expression of TN-C and the intensity of lymphocytic infiltrate and the severity of pruritus were demonstrated. Dermal TN-C expression is significantly elevated in hypertrophic LP cases and in cases with leg lesions. Epidermal expression of TN-C showed no significant correlation with any of the clinical or pathological features. Conclusion Prominent TN-C expression in LP lesions magnifies its role in the pathogenesis of this disease.

The role of mast cells and mast cell tryptase in skin tags: an immunohistochemical study

Objective The aim of this study was to assess mast cell tryptase (MCT) expression in skin tags (STs) in comparison with normal skin. Background STs or acrochordons are common benign connective tissue of the dermis that are composed of loose fibrous tissue, in middle-aged and elderly individuals, located predominantly in intertriginous skin and neck, which consists of a bit of skin projecting from the surrounding skin. Patients and methods This study was carried out on 30 patients and 10 control participants. One biopsy was obtained from each patient. Mast cell count and mast cell density were assessed by immunohistochemical staining for MCT and expressed as mean, median, and range (the average mast cell count/high-power field). Results The results of the present study showed a statistically significant increase in the mast cells count in STs in comparison with normal skin. Conclusion Higher expression of MCT in ST compared with normal skin and this enzyme mediator may be responsible for induction of fibrosis in ST.