Serum and Tissue Lipocalin-2 Expression in Chronic Kidney Disease Pruritic Patients.

BACKGROUND: Uremic pruritus is an irritating symptom for patients with end-stage kidney disease. Lipocalin-2 (LCN2) has relevant importance in several biological cellular processes and immunity. It is also a major player in the progression of many disorders, such as renal injury. AIM: To evaluate LCN2 expression in chronic kidney disease (CKD) pruritic patients in serum together with immunohistochemical expression in skin samples and further correlation of their results with the studied clinicopathologic parameters. MATERIALS AND METHODS: Serum level of LCN2 (assessed by enzyme-linked immunosorbent assay) and skin immunohistochemical expression were investigated in 25 CKD patients and 25 healthy controls. Ten patients were subjected to narrowband ultraviolet B phototherapy for 12 weeks then re-evaluated for serum and tissue LCN2 after therapy. RESULTS: LCN2 expression was increased significantly in both the epidermis and dermal adnexa in CKD patients over controls. Also, serum LCN2 level was higher in patients than in healthy subjects and was significantly associated with itching severity, grades of CKD, urea, and creatinine serum level. Tissue and serum levels of LCN2 were significantly diminished in CKD patients following narrowband therapy along with improvement of the severity of pruritus. CONCLUSIONS: The increased serum and tissue LCN2 expression in CKD pruritic patients and its pronounced decrease, in addition to the improvement of pruritus after treatment, suggest a major pathogenic role of LCN2 in uremic pruritus.

Circulating and/or cutaneous irisin resistance: A novel link among androgenetic alopecia, comorbid metabolic syndrome and cardiovascular risks.

BACKGROUND: Androgenetic alopecia (AGA) is a common cause of hair loss in both genders that may be associated with disturbed systemic metabolism. Irisin is a hormone-like myokine that greatly influences systemic metabolism and is linked to cardiovascular diseases. AIM: To detect irisin role in AGA and its associated metabolic syndrome (MetS) and cardiovascular risk. PATIENTS/METHODS: This case-control study included 44 AGA patients of both genders and 22 healthy individuals. Serum irisin level was measured using ELISA and scalp biopsy was taken to detect irisin immunohistochemically. Carotid Doppler ultrasonography was performed to measure carotid intima media thickness (CIMT). RESULTS: Higher serum irisin was significantly detected in AGA patients (p ˂ 0.001), and in males (p = 0.01) particularly severe cases (p ˂ 0.001). It was significantly higher in AGA patients presenting with MetS and those suffering from dyslipidemia (p ˂ 0.001 for both). Multivariate regression analysis proved BMI (p = 0.01) and serum irisin (p = 0.02) as independent predictors of CIMT abnormality among AGA patients. Regarding cutaneous irisin expression, the epidermal H-score was significantly higher in AGA patients with MetS compared to those without (p = 0.04). Epidermal H-score ˃100 was significantly associated with male gender (p = 0.05), severe AGA (p = 0.02), MetS (p = 0.03), dyslipidemia (p = 0.03), and abnormal CIMT (p = 0.03). CONCLUSION: High serum irisin and upregulated epidermal irisin expression are associated with the incidence of MetS, dyslipidemia, and CIMT abnormality among AGA patients. This may indicate resistance to irisin, which hinders its favorable cardiometabolic actions. Further studies are warranted to investigate the concept of irisin resistance in AGA patients, which was uniquely discussed in the present study.

Immunohistochemical expression of Axin-2, as an implication of the role of stem cell in scar pathogenesis and prognosis.

BACKGROUND: Wound healing is a multi-phased process. A disruption in these phases could result in a persistent wound or an atypical scar. Wounding activates wingless proteins (Wnt) signaling, which aids in the healing process. Axis inhibition protein-2 regulates a variety of cellular activities through the Wnt and other pathways. AIM: To assess the role of Axin-2 in patients with abnormal scars, using immunohistochemical study. METHODS: This case-control study enrolled a total of 60 participants: 30 patients with abnormal scars (12 hypertrophic scars, 13 atrophic scars, and 5 keloid scars) and 30 age, sex, and site matched, apparently healthy controls. For immunohistochemistry examination of Axin-2 expression, skin samples were obtained from (i) lesional and (ii) perilesional skin of patients with aberrant scars, as well as (iii) normal control's skin. RESULTS: Epidermal Axin-2 expression positivity, cellular topography, intensity, and H score showed significant differences between the groups (p < 0.05). In the dermis (fibroblast/myofibroblast), there were significant differences in Axin-2 expression positivity, location, intensity, and H score (p < 0.001 for all). The epidermal Axin-2 H score and the Manchester scale had a significant positive correlation (r = 0.832, p = 0.001). The epidermal Axin-2 H score and age (r = -0.576, p = 0.001), and the Stony Brook scale (r = -0.419, p = 0.021), had significant negative correlations. CONCLUSION: Axin-2 overexpression might be accused in pathogenesis of abnormal scar and clinical worse scar outcome. In order to deprive scars of their regenerative cell pools, future scar therapies may target Axin-2 as a stem cell marker.

Krox20 expression in abnormal scars: An immunohistochemical study.

BACKGROUND: Scars are the end outcome of healing. They are grouped into several types, the common of which are keloids, hypertrophic, and atrophic scars. The role of Krox20 in skin and hair physiology and pathology had emerged. Overexpression of Krox20 was sufficient to stimulate collagen gene expression and myofibroblast differentiation and is necessary for transforming growth factor-ß (TGF-ß) induced profibrotic responses. OBJECTIVE: To investigate the role of Krox20 in abnormal scar pathogenesis. Hopefully, this insight can set the route for newer therapeutic approaches. MATERIALS AND METHOD: This study was carried out on 30 cases (10 cases of keloids, 10 cases of atrophic scars, and 10 cases with hypertrophic scars [HTS]) and 10 age and gender-matched apparently healthy subjects as a control group. Thirty biopsies were taken from perilesional areas. Evaluation of Krox20 expression was done using standard immunohistochemical technique. RESULTS: Krox20 was downregulated in epidermis of scar biopsies compared with perilesional and normal skin (p = 0.02) while it was overexpressed in fibroblasts in lesional scar biopsies compared with perilesional and normal skin (p < 0.001). Keloid cases have significantly higher Krox20 expression in fibroblasts compared with HTS cases (p < 0.001). Krox20 had significantly nucleocytoplasmic pattern of staining in scar cases compared with normal skin (p < 0.001). CONCLUSION: Krox20 overexpression may have a role in scar pathogenesis through upregulation of multiple genes associated with tissue remodeling and wound healing. This may open an avenue for research for new therapies based on Krox20 inhibition.

Vitamin D Receptor Gene Polymorphisms Taq-1 and Cdx-1 in Female Pattern Hair Loss.

BACKGROUND: Female pattern hair loss (FPHL) is an important cause of hair loss in adult women and has a major impact on patient's quality of life. It evolves from the progressive miniaturization of follicles that leads to a subsequent decrease of hair density, leading to non-scarring diffuse alopecia, with characteristic clinical, dermoscopic, and histological patterns. Vitamin D receptor (VDR) is expressed in follicular keratinocytes and dermal papilla cells and is shown to have important role in hair growth and regulation of hair cycle. VDR polymorphism was not extensively investigated in hair disorders including FPHL. AIM: To investigate the association between VDR gene polymorphism (Cdx-1 and Taq-1) and FPHL to explore if these polymorphisms affect the disease occurrence or influence its clinical presentation. METHODS: A case-control study was conducted on 30 female patients with FPHL and 30 age-matched female healthy subjects, as a control group. Degree of hair loss was assessed by Ludwig grading. VDR gene polymorphisms, Taq-1 and Cdx-1 were investigated by real time polymerase chain reaction. RESULTS: CC genotype, TC genotype, and T allele of Taq-1 were more prevalent in FPHL patients than in control group. They increased disease risk by 12.6, 2.1, and 2.9 folds, respectively. AA genotype, GA genotype, and G allele of Cdx-1 were significantly more prevalent among FPHL patients than in control group. They increased disease risk by 7.5, 5.2, and 5.5 folds, respectively. CONCLUSION: Taq-1 and Cdx-1 can be considered as risk factors for FPHL. They may play role in disease persistence rather than disease initiation. This association may be explained by failure of new anagen growth and decreased proliferation of hair follicle stem cells. Further studies are recommended to confirm current findings.

Vitamin D Receptor Gene Polymorphism In Chronic Telogen Effluvium; A Case-Control Study.

BACKGROUND: Telogen effluvium (TE) is a form of alopecia characterized by diffuse hair shedding. Vitamin D receptor (VDR) plays a role in hair cycle regulation as it is expressed in follicular keratinocytes and dermal papilla cells. PURPOSE: To investigate the association between Cdx1 and Taq1 VDR gene polymorphisms and chronic TE. METHODS: Thirty female patients with chronic TE were selected and 30 healthy, age- and sex-matched volunteers were included as a control group. Detection of VDR gene polymorphisms Taq1 and Cdx1 was done by real-time polymerase chain reaction. RESULTS: Regarding Taq 1, CC genotype was present in 30% of cases versus 3.3% of controls. TC genotype was present in 33.3% of cases and 36.7% of controls. CC genotype was significantly associated with cases (P=0.01). It increases the risk of chronic TE by 14.7 folds. C allele was significantly associated with patient group (P=0.004). It increases the risk of disease occurrence by 3.1 folds. Regarding Cdx1, AA genotype was present in 6.7% of cases versus 3.3% of controls. GA genotype was present in approximately 30% of cases and 6.7% of controls. GA genotype was significantly associated with cases (P=0.03). It increases the risk of chronic TE by 6.3 folds. A allele was significantly associated with patient group (P=0.007). It increases the risk of disease occurrence by 3.8 folds. LIMITATIONS: The main limitation is the small number of cases due to the time and financial constraints. Only chronic TE was analyzed, therefore, other types should be investigated in the following studies. CONCLUSION: After exposure to primary physical or mental stressor, hair follicles are stimulated to enter prematurely into telogen and shed out. In individuals with Taq1 and Cdx1 polymorphisms, the disease persists as a result of prevention of new anagen growth and inhibition of hair follicle stem cell proliferation.

Peroxisome Proliferator-Activated Receptor-γ Gene Polymorphism in Psoriasis and Its Relation to Obesity, Metabolic Syndrome, and Narrowband Ultraviolet B Response: A Case-Control Study in Egyptian Patients.

BACKGROUND: Psoriasis is a common dermatologic disease with multifactorial etiology in which genetic factors play a major role. Peroxisome proliferator-activated receptor (PPAR)-γ is expressed in keratinocytes and is known to affect cell maturation and differentiation in addition to its role in inflammation. AIM: To study the association between PPAR-γ gene polymorphism and psoriasis vulgaris in Egyptian patients to explore if this polymorphism influenced disease risk or clinical presentation. METHODS: Forty-five patients with psoriasis vulgaris and 45 age, sex and body mass index matched healthy volunteers who have no present, past or family history of psoriasis as a control group were enrolled. Selected cases included obese and nonobese participants. Detection of PPAR-γ gene polymorphism was done with restriction fragment length polymorphism polymerase chain reaction. Narrow-band ultraviolet B (NBUVB) was given for every case three times/week for 12 weeks. RESULTS: Homopolymorphism, heteropolymorphism, and Ala allele were significantly associated with cases (P = 0.01, P = 0.01, and P = 0.004, respectively) and increased risk of occurrence of psoriasis by 5.25, 3.65, and 3.37 folds, respectively. Heteropolymorphism was significantly associated with nonobese cases compared to obese ones (P = 0.01). Ala allele was significantly associated with obese cases (P = 0.001) and increased risk of occurrence of psoriasis in obese participants by 1.14 folds. Homopolymorphism, heteropolymorphism, and Ala allele were more prevalent among obese cases without metabolic syndrome (MS) than obese cases with MS but without statistical significance. Percentage of decrease of mean Psoriasis Area and Severity Index score before and after 3 months of treatment with NBUVB was higher in cases with heteropolymorphism with no significant difference between homo- and heteropolymorphism. CONCLUSION: PPAR-γ gene polymorphism is associated with and increased the risk of psoriasis and its associated obesity in Egyptian patients. It has no role in NBUVB response in those patients. Future large-scale studies on different populations are recommended.

Polymorphism of FAS and FAS Ligand Genes in Alopecia Areata: A Case-control Study in Egyptian Population.

BACKGROUND: Alopecia areata (AA) is a common dermatologic disease with suspected autoimmune etiology. Tumor necrosis factor superfamily member 6 or CD95 (FAS) and FAS ligand (FASL) are proapoptotic proteins. The relationship between apoptosis and autoimmunity is well recognized. Inflammatory T cells in AA are cytotoxic and possess FAS/FASL antigens. AIM: This study aims to investigate the association between FAS-670 A/G and FASL-124 A/G gene polymorphisms and AA to clarify if these polymorphisms influence disease occurrence or increase disease risk. MATERIALS AND METHODS: A case-control study was conducted on sixty patients with AA, and 40 age- and sex-matched healthy subjects, as a control group. Disease severity was assessed by severity of alopecia tool (SALT) Score. FAS 670A/G and FASL 124A/G gene polymorphisms were investigated by the restriction fragment length polymorphism polymerase chain reaction. RESULTS: For FAS gene, G/G genotype was significantly higher in cases than in control group with odds ratio 5.1. G allele was more prevalent among patient group with odds ratio 1.75. For FASL gene, A/G genotype was significantly higher in cases than in control group with odds ratio 4.53. G allele was more prevalent among patient group with odds ratio 1.88. GG genotype of FAS was significantly associated with longer disease duration (P =0.001), recurrent attacks (P =0.01), higher SALT score (P =0.009), alopecia universalis (P =0.002), and severe disease (P =0.006). CONCLUSION: FAS and FASL gene polymorphisms are associated with AA. Further large-scale studies on different ethnicities are required for more clarification of their role in disease development. Therapeutic modalities based on their inhibition could be promising in the treatment of a common disease like AA.

Identification of Genotypes and Allelic Frequencies of Vitamin D Receptor Gene Polymorphism (TaqI) in Egyptian Melasma Patients.

BACKGROUND: Melasma is a characteristic pattern of facial hyperpigmentation, occurring primarily on the forehead, cheeks, and chin, in a mask-like distribution. The pathogenesis of melasma is not fully understood. Vitamin D plays a role in skin pigmentation. It exerts its effect through vitamin D receptor (VDR), which is expressed in variable cells including normal melanocytes. AIM AND OBJECTIVE: The aim of the current work was to investigate if VDR gene polymorphism (TaqI) confers susceptibility to melasma in Egyptian patients. MATERIALS AND METHODS: A total of 45 female patients with melasma were recruited and 50 healthy subjects that were matched on age, sex, body mass index, and skin phototype, were included as a control group. TaqI polymorphism was investigated using restriction fragment length polymorphism polymerase chain reaction (RFLP PCR). RESULTS: Presence of (t) allele and (tt) genotype was significantly associated with melasma cases compared with control group (P < 0.001 for both). No significant association was found between (tt) genotype or (t) allele and clinical data of the studied cases. CONCLUSION: TaqI polymorphism is associated with melasma. Further, large-scale studies are recommended to underscore and validate the current findings. It is also necessary for future studies to extend the research to other populations and ethnicities. Investigating other VDR gene polymorphisms in melasma is also warranted. Since melasma is a multifactorial disease, gene-gene and gene-environment interactions should be considered in future genetic-epidemiologic researches to apply more comprehensive insight into the role of VDR gene in its pathogenesis.

Evaluation of Hypoxia Inducible Factor-1α and Glucose Transporter-1 Expression in Non Melanoma Skin Cancer: An Immunohistochemical Study.

INTRODUCTION: Hypoxia Inducible Factor-1 (HIF-1) is a mediator enabling cell adaptation to hypoxia. It plays its role mainly through transcription of many target genes including Glucose Transporter-1 (GLUT-1) gene. AIM: The present work aimed at evaluating the pattern and distribution of HIF-1α and GLUT-1 in each case and control. MATERIALS AND METHODS: A case-control and retrospective study was conducted on archival blocks diagnosed from pathology department as, Basal Cell Carcinoma (BCC, 20 cases), cutaneous Squamous Cell Carcinoma (SCC, 20 cases) and 20 normal site-matched skin biopsies from age and gender-matched healthy subjects as a control. Evaluation of both HIF-1α and GLUT1 expression using standard immunohistochemical techniques was performed on cut sections from selected paraffin embedded blocks. RESULTS: HIF-1α was expressed in 90%, 35% and 100% of normal skin, BCC and SCC tumour islands respectively. It was up regulated in both BCC and SCC compared with normal skin (p= 0.001, p<0.001 respectively). GLUT-1 was expressed in 100%, 70% and 100% of normal skin, BCC and SCC tumour islands respectively. It was down regulated in Non Melanoma Skin Cancer (NMSC) cases compared with normal skin (p=0.004). HIF-1α and GLUT-1 localization in tumour nests was central, peripheral or central and peripheral. Both HIF-1α and GLUT-1 showed variable expression in stroma, adnexa and inflammatory cells. No significant correlation was found between Histo (H) score or expression percentage values of HIF-1α and those of GLUT-1 in tumour islands or in overlying epidermis either in BCC or SCC. CONCLUSION: HIF-1α may have a role in NMSC pathogenesis through adaptation to hypoxia which results from excessive proliferation. GLUT-1 down regulation in NMSC may be explained by its consumption by proliferating tumour cells. The expression of HIF-1α and GLUT-1 in normal epidermis, stromal and adnexal structures needs further research.

Is Aquaporin-3 a Determinant Factor of Intrinsic and Extrinsic Aging? An Immunohistochemical and Morphometric Study.

Aquaporin-3 (AQP3) is an aquaglyceroporin that plays a role in skin hydration, cell proliferation, and migration. The aim of this work was to investigate the expression of AQP3 in sun-exposed and sun-protected human skin from different age groups to understand the relationship between AQP3 and skin aging. Using standard immunohistochemical techniques, sun-exposed and sun-protected skin biopsies were taken from 60 normal individuals. AQP3 was expressed in the basal and the suprabasal layers, sparing the stratum corneum, in all specimens. Dermal expression was detected in fibroblasts, endothelial cells, and adnexa. Sun-protected skin showed a significantly higher epidermal H-score and percentage of expression (P=0.002 and <0.001, respectively) compared with sun-exposed skin. The AQP3 expression intensity showed a gradual decrease from the 20 to 35-year-old group to the 35 to 50-year-old group, with the least immunoreactivity in the above 50-year-old group. A significant difference was detected in the H-score in favor of the 20 to 35-year-old group in sun-exposed and sun-protected skin (P<0.001 for both). A significant negative correlation was noted between the AQP3 expression percentage and the age in sun-exposed (r=-0.64, P<0.001) and sun-protected skin (r=-0.53, P<0.001). In conclusion, the skin dryness observed in intrinsic and extrinsic aged skin may be explained, at least in part, by AQP3 downregulation. This may open new avenues sufficient to control skin texture and beauty. Its interaction in skin protein organization and gene polymorphism can also be tackled in future research. In addition, clinical trials using AQP3 topical applications should be carried out to evaluate its effectiveness in the reversal of age-related skin changes.

Intrinsic versus Extrinsic Aging: A Histopathological, Morphometric and Immunohistochemical Study of Estrogen Receptor ß and Androgen Receptor.

Skin is a target organ of sex steroids which play important roles in skin health and disease. The aim of this study is to investigate the expression of estrogen receptor ß (ERß) and androgen receptor (AR) in human skin from different age groups for a better understanding of the hormonal regulation of skin aging. Using standard immunohistochemical techniques, biopsies of sun-unprotected and sun-protected skin were taken from 60 normal subjects. Sun-protected skin showed significantly higher immunoreactivity for ERß and AR compared to sun-unprotected skin of all age groups. Significantly higher ERß H score and percent of expression were associated with the 20-35 years age group compared to the groups that were 35-50 years and >50 years old (p < 0.02, p = 0.03, respectively) in sun-unprotected and sun-protected skin (p < 0.001, p = 0.01, respectively). AR H score showed a negative correlation with age (p = 0.04) with no significant difference in immunoreactivity in different age groups, either in sun-unprotected or sun-protected skin. There was also a significant correlation between ERß H score and epidermal thickness in sun-unprotected (p = 0.04) and sun-protected skin (p = 0.04) in studied subjects regardless of age. The same relationships did not reach significance with AR expression. However, a significant positive correlation was detected between H scores and percent of expression of ERß and AR in sun-unprotected (p = 0.01, p = 0.02, respectively) and sun-protected skin (p = 0.005, p = 0.02, respectively) regardless of age. In conclusion, both ERß and AR decline gradually with intrinsic and extrinsic aging. This decline is more obvious with extrinsic aging. Further large-scaled studies are recommended to expand, validate and translate current findings to clinically significant, diagnostic and therapeutic applications. Molecular studies to investigate the probable ligand-independent action of both receptors are warranted. In addition, their gene expression patterns and associated signaling and metabolic pathways can also be tackled to provide a basis for further interventions in pathological processes that involve their dysregulation.

Immunohistochemical Evaluation of Leptin Expression in Wound Healing: A Clue to Exuberant Scar Formation.

Leptin has been recognized as an important factor for promoting normal cutaneous wound healing. The aim of this work was to explore leptin expression in keloid and hypertrophic scars (HS) compared with surgical scars and normal skin. The relationship of this expression with clinicopathologic parameters of studied cases was also evaluated. Using immunohistochemical techniques, leptin was analyzed in skin biopsies of 60 nonobese subjects without metabolic syndrome who presented with keloids (20), HS (20), and surgical scars (20). Twenty normal skin samples, from age-matched, sex-matched, and body mass index-matched subjects, were enrolled as a control group. Leptin showed positive immunoreactivity in epidermis in all cases of surgical scars and keloids and in 75% of HS cases. Dermal expression in fibroblasts, inflammatory cells, and endothelial cells was positive in all cases of surgical scars and keloids and in 70% of HS cases. Leptin was overexpressed in keloids and HS compared with normal skin in epidermis (P<0.001 for both) and dermis (P<0.001 for both) and to surgical scars both in epidermis (P=0.0006, P=0.01, respectively) and dermis (P=0.0001, P=0.001, respectively). Higher leptin H score was significantly associated with older age (P=0.02) and positive family history (P=0.002) in keloid cases and with axial site in keloid and HS cases (P=0.001, P=0.02, respectively). Significant positive correlation was noted between epidermal and dermal leptin H scores in keloids (r=+0.37, P=0.04) and HS (r=+0.39, P=0.02). This may be due to epithelial-mesenchymal interactions in scar pathogenesis. In conclusion, in situ leptin overexpression may increase the possibility of keloid and HS occurrence through altered cytokine production and prolonged healing phases with excessive deposition and delayed collagen degradation. This may open an avenue for research for new therapeutic modalities based on its inhibition.

Homozygous Familial Hypercholesterolemia Associated with Symmetric Subcutaneous Lipomatosis.

Homozygous familial hypercholesterolemia is an autosomal dominant disorder of lipid metabolism, characterized by reduced clearance of low-density lipoprotein-cholesterol and a high risk of rapid development of cardiovascular diseases. Its incidence is relatively rare and estimated to be one in one million in general populations. Here, we report homozygous familial hypercholesterolemia in two Egyptian young siblings, presented with cutaneous, tendinous xanthomas, and corneal arcus. One of them has symmetric subcutaneous lipomatosis, which has not been reported before in association with familial hypercholesterolemia.

Evaluation of Aquaporin-3 Role in Nonmelanoma Skin Cancer: An Immunohistochemical Study.

Aquaporin-3 (AQP3), is an aquaglyceroporin, that plays a role in cell proliferation, tumorigenesis, and cell migration. This study aimed at evaluating the possible role of AQP3 in nonmelanoma skin cancer (NMSC) pathogenesis through its immunohistochemical expression in skin biopsies of these diseases. One-hundred and thirty cutaneous specimens were studied. These included 60 cases of NMSC and 40 normal skin and 30 psoriasis samples, from age- and gender-matched subjects, as a control group. AQP3 was expressed in 66.7% of basal cell carcinoma (BCC) cases and in 93.3% of squamous cell carcinoma (SCC) cases. Higher AQP3 expression (p = .01), expression percentage (p = .01), and H score (p = .04) were significantly associated with SCC compared to BCC. Normal skin and psoriasis showed significantly higher AQP3 expression (p = .001, p < .001, respectively), expression percentage (p < .001 for both), and H score values (p < .001, p = .001, respectively) compared to NMSC. Higher H score values in BCC were significantly associated with female gender (p = .02) and with nodular lesions (p > .001). Higher H score values in SCC were significantly associated with grade III tumors (p = .04) and AQP3 percentage of expression was significantly correlated with grade III tumors (r = .48, p = .009). In conclusion, AQP3 may play a role in NMSC pathogenesis. This probably occurs through aquaporin-mediated glycerol transport and ATP generation. Its downregulation, observed in the current work, is mostly a result of excessive proliferation. Further studies are needed to investigate the therapeutic effect of its inhibition in NMSC treatment.

Immunohistochemical Evaluation of Leptin Role in Skin Tags.

Skin tags (STs) are common benign dermal connective tissue neoplasms that are mainly composed of loose fibrous tissue. However, their exact etiology is not fully understood. Leptin is a major player in the biology and pathology of the skin and its appendages. It is linked to cell differentiation, proliferation, migration, and survival with pronounced effects on angiogenesis, blood flow, and tissue perfusion. This study aimed at investigating the possible role of leptin in STs pathogenesis and correlating its expression with different clinical and histopathological parameters. Using immunohistochemical techniques, we examined 90 subjects. These included 60 non-obese cases with STs and 30 age-, gender- and Body Mass Index-matched normal subjects as a control group. Leptin was overexpressed in STs compared with normal skin (p < .001). Nuclear and nucleocytoplasmic patterns were significantly associated with cases both in epidermis (p < .04) and dermis (p < .001). Higher epidermal leptin H score was significantly associated with female gender (p = .004) and haphazard collagen arrangement (p < .03). Higher dermal leptin H score was significantly associated with smooth skin tags (p = .01), dilated blood vessels (p = .04), presence of mast cells (MCs) (p = .002), presence of inflammatory cells (p = .004), and haphazard collagen arrangement (p < .001). In conclusion, leptin may play a role in STs pathogenesis through its effects on keratinocytes, fibroblasts and vascular endothelium. Further studies are recommended to clarify the molecular interplay between leptin and MCs in ST pathogenesis. Further studies are also needed to determine the significance of its nuclear expression.

Immunohistochemical expression of sperm-associated antigen 9 in nonmelanoma skin cancer.

Sperm-associated antigen 9 (SPAG9) is a scaffold protein for c-Jun-NH2-kinases, which play an important role in cell survival, proliferation, apoptosis, and tumor development. SPAG9 was claimed to be involved in the pathogenesis of carcinoma in different organs. The aim of this work was to investigate its role in the pathogenesis of nonmelanoma skin cancer (NMSC) through its immunohistochemical (IHC) localization in skin biopsies of these tumors. This retrospective and prospective study included 67 cutaneous specimens; 42 of NMSC [20 cases with basal cell carcinoma (BCC) and 22 cases with squamous cell carcinoma (SCC)] and 25 normal sun-exposed skin biopsies from age and gender-matched healthy subjects as a control group. SPAG9 expression was evaluated using standard IHC techniques. SPAG9 was expressed in 90% of BCC cases and in 81.8% of SCC cases. Positive expression in inflammatory cells was detected in 100% and 63.6% of BCC and SCC cases, respectively. Positive stromal expression was detected in 20% of BCC cases and was absent in all SCC cases. A significant negative correlation (r = -0.55, P = 0.008) was noted between SPAG9 H score and SCC histological grade and a significant association between SPAG9 H score and tumor grade was also detected where higher values were present in grade I tumors (P = 0.001). SPAG9 was upregulated in NMSC when compared with normal skin. In conclusion, SPAG9 is expressed in NMSC cases. It should be evaluated in large-scale studies to determine if it plays an active pathogenic role or its expression is an epiphenomenon not related to NMSC pathogenesis. Large-scale studies are warranted to determine its potential utility in guiding treatment decisions and following disease progression in theses cases. Its expression in normal skin needs further investigation.

Toll-like receptor 2 and P. acnes: do they trigger initial acne vulgaris lesions?

OBJECTIVE: To elucidate the role of toll-like receptor 2 (TLR2) in the pathogenesis of acne vulgaris through its immunohistochemical localization in inflammatory and noninflammatory lesions of this disease entity. STUDY DESIGN: Using standard immunohistochemical techniques, we examined 30 acne cases (involved and noninvolved skin) and the normal skin biopsies of 30 sex- and age-matched, healthy subjects representing the control group. RESULTS: All examined cases showed positive TLR2 expression in epidermis, pilosebaceous units and dermal inflammatory infiltrate. There were statistically significant differences between acne-involved skin and normal skin and between acne-involved and noninvolved skin regarding TLR2 expression intensity in pilosebaceous units (p < 0.001 for both) and dermal inflammatory infiltrate (p < 0.001 for both). Intense TLR2 expression was in favor of inflammatory acne lesions in pilosebaceous units (p = 0.03) and dermal inflammatory infiltrate (p < 0.05). Intense TLR2 expression was also in favor of severe acne lesions in pilosebaceous units (p = 0.0002) and dermal inflammatory infiltrate (p = 0.001). CONCLUSION: TLR2 is involved in the pathogenesis of inflammatory and noninflammatory acne lesions. This occurs through Propionibacterium acnes-mediated activation with the resultant release of inflammatory cytokines.

Immunohistochemical expression of aberrant Notch-1 signaling in vitiligo: an implication for pathogenesis.

The etiopathogenetic mechanisms leading to pigment loss in vitiligo are not fully understood. Notch signaling is required for development and maintenance of melanocyte lineage and acts as a key component among keratinocyte-melanocyte interactions. The current study aimed to investigate the possible role of Notch signaling and its effect on the whole melanocyte lineage in vitiligo and correlating it with the different clinicopathologic parameters. Using immunohistochemical technique, Notch-1 expression was evaluated in 50 lesional and 20 perilesional biopsies of patients with vitiligo in comparison with 20 normal skin biopsies as a control group. Lesional biopsies were stained with human melanoma black-45 and tyrosinase-related protein-2 to demonstrate the melanocyte lineage. Membranous and/or nuclear expression of Notch-1 was in favor of control and perilesional skin, whereas cytoplasmic expression appeared only in vitiliginous lesions (P < .05). Membranous and/or nuclear expression of Notch-1 was significantly associated with epidermal human melanoma black-45 positivity (P = .01) and percentage of expression in both epidermis (P = .02) and hair follicles (P = .03) of lesional skin. Cytoplasmic pattern of Notch-1 expression in epidermis was significantly found in lesions with white hair (P = .04) and in cases with marked keratinocyte vacuolization (P = .03). Segmental and acrofacial vitiligo were associated with mild to moderate Notch-1 intensity, whereas generalized vitiligo was associated with strong intensity of expression (P = .02). In conclusion, Notch-1 signaling is inactivated in vitiligo with consequent loss of epidermal and/or follicular active melanocytes. Aberrant Notch signaling in vitiliginous white hair and acral and segmental vitiligo may be the cause of their treatment resistance.