Immunolocalization of glioma-associated oncogene homolog 1 in non melanoma skin cancer.

Glioma-associated oncogene homolog (GLI)1 is involved in controlling cell proliferation and angiogenesis. The aim of this work was to explore its possible role in non-melanoma skin cancer pathogenesis through its immunohistochemical (IHC) expression in skin biopsies of these diseases and correlating this expression with the clinico-pathological parameters of the studied cases. Seventy-six cutaneous specimens were studied; 30 cases with basal cell carcinoma (BCC), 30 cases with squamous cell carcinoma (SCC) and 16 normal skin samples, from age- and gender-matched subjects, as a control group. GLI1 was expressed in all BCC cases and in 60% of SCC cases. All SCC cases showed cytoplasmic, while 70% of BCC cases showed nucleocytoplasmic immunoreactivity. It was over expressed in BCC and SCC compared to normal skin (p = 0.01 and 0.0006, respectively). Higher Histo (H) score in BCC cases was significantly associated with female gender (p = 0.04), multiple lesions, desmoplastic stromal reaction and stromal angiogenesis (p < 0.001 for all). Higher H score in SCC cases was significantly associated with scalp location, nodular type, recurrent lesions, high tumor grade, lymphovascular invasion (p = 0.004 for all), inflammatory stromal reaction (p = 0.01), lymph node involvement and absence of calcification (p = 0.001 for both). In conclusion, GLI1 may play a role in BCC pathogenesis through its role in cell proliferation, migration, and angiogenesis. Its upregulation and cytoplasmic localization in SCC may suggest that its role in tumor pathogenesis is through mechanisms other than Hedgehog pathway activation. Further studies are needed to clarify the exact molecular basis of its oncogenic action.

Nuclear factor kappa B and cyclo-oxygenase-2: two concordant players in psoriasis pathogenesis.

Nuclear factor kappa B (NFκB) is a key regulatory element in a variety of immune and inflammatory pathways, cellular proliferation, differentiation and apoptosis. Cyclo-oxygenase 2 (COX2) is one of the downstream targets of NFκB. The current work aimed to explore the possible role of NFκB and COX2 in psoriasis pathogenesis through their immunohistochemical (IHC) expression in skin biopsies of this disease and correlating this expression with clinico-pathological parameters of studied cases. 103 subjects were studied; including 58 cases with psoriasis vulgaris (lesional and perilesional skin) and 45 normal, age- and gender-matched subjects, as a control group. NFκB and COX2 expressions were evaluated using standard IHC techniques. NFκB and COX2 were upregulated in psoriasis lesional skin compared to perilesional (p < 0.001 for both) and control skin (p < 0.001 for both). Higher NFκB and COX2 H scores were significantly associated with absent granular cell layer (p = 0.02 for both), severe degree of perivascular inflammatory infiltrate (p = 0.03 and 0.002, respectively) and thin suprapapillary epidermis (p = 0.003 and 0.006, respectively). Significant positive correlation was noted between NFκB and COX2 H scores in epidermis (r = 0.41, p = 0.02) and dermis (r = 0.6, p = 0.04) of lesional skin. Significant positive correlation between NFκB H score and PASI score (r = 0.38, p = 0.04) and between COX2 H score and PASI score (r = 0.52, p < 0.001) were detected in lesional epidermis. In conclusion, both NFκB and COX2 play a role in the pathogenesis of chronic plaque psoriasis. This may open an avenue for research for new therapeutic modalities based on their inhibition.

Immunolocalization of androgen receptor and estrogen receptors in skin tags.

Skin tags (STs) are benign connective tissue tumors of the dermis. Several clinical observations suggested the involvement of sex steroids in their development. This study aimed at investigating the possible role of androgen receptor (AR) and estrogen receptors (ERs) in STs pathogenesis through their immunohistochemical (IHC) localization in skin biopsies of this disease and to correlate their expression with different clinical and histopathological parameters. Using IHC techniques, we examined 62 cases with STs and 30 gender- and age-matched, healthy subjects, representing the control group. ERα, ERß, and AR were upregulated in STs compared to normal skin in epidermis and dermis (p < .001 for all). Higher AR H score was significantly associated with axillary STs (p = .02), skin colored tags (p = .03), acanthosis, and papillomatosis (p = .04 for both). Higher ERα H score was significantly associated with hyperpigmented tags (p < .001) and positive family history (p = .003). Higher ERß H score was significantly associated with female gender and obesity (p = .004 for both). Higher ERα and AR H scores were significantly associated with loose collagen arrangement (p = .02, p = .004, respectively). Higher AR, ERα, and ERß H scores were significantly associated with the presence of mast cells (p = .01, p = .04, p = .002, respectively) and dilated blood vessels (p = .006, p = .04, p = .04, respectively). In conclusion, AR and ERs may share in STs pathogenesis through their effect on keratinocytes, fibroblasts, and mast cells.

Androgenetic alopecia, metabolic syndrome, and insulin resistance: Is there any association? A case-control study.

CONTEXT: Although several previous studies have investigated the association of metabolic syndrome (MS) and insulin resistance (IR) with androgenetic alopecia (AGA), the results have been inconsistent. AIM: We attempted to assess the presence of MS and IR in patients with AGA. This may help to detect if AGA can be considered as a clue for underlying serious systemic diseases. MATERIALS AND METHODS: One hundred male patients with stages III-VII AGA, in Hamilton-Norwood classification, and 100 normal, gender- and age-matched control subjects were included. Anthropometric measures, blood pressure, fasting glucose, fasting insulin, high-density lipoprotein cholesterol, and triglycerides were measured for the all participants. The presence of MS and IR was evaluated. RESULTS: There were statistically significant differences regarding mean values of body weight (P < 0.001), height (P = 0.002), waist circumference (P < 0.001), body mass index (P < 0.001), systolic (P < 0.001), and diastolic blood pressure (P < 0.001), fasting glucose (P < 0.001), triglycerides (P < 0.001), high-density lipoprotein cholesterol (P < 0.01), fasting insulin (P = 0.02) and homeostasis model assessment of insulin resistance (P < 0.001) between cases and controls. A statistically significant association was found between AGA and MS (P = 0.002) and between AGA and IR (P < 0.001). Multiple logistic regression analysis revealed that waist circumference (>102 cm) was the most significant risk factor for developing MS. It increased the risk of MS by 1.25-folds (95% CI = 1.10-1.42, P < 0.001). CONCLUSION: Our results support the recommendation for assessing MS and IR in all young males with stage III or higher AGA. Early intervention is critical to reduce the risk and complications of cardiovascular disease and type 2 diabetes mellitus later in life.

Oxidative stress in alopecia areata: a case-control study.

BACKGROUND: Increased reactive oxygen species (ROS) and lipid peroxidation are seen in many dermatologic disorders, including atopic dermatitis, psoriasis, vitiligo, acne vulgaris, pemphigus vulgaris, and lichen planus. In alopecia areata (AA), there is increased production of ROS from perifollicular inflammatory cells. OBJECTIVE: The aim of this study was to determine the oxidative stress index (OSI) and lipid peroxidation by studying serum total oxidant capacity (TOC), total antioxidant capacity (TAC), and malondialdehyde (MDA) values in AA patients. METHODS: The study included 35 AA patients and a control group consisting of 30 age- and sex-matched healthy volunteers. The serum TOC, TAC, and MDA values were measured, and the OSIs were calculated and compared in both groups. RESULTS: The mean serum TOC (p < 0.001), MDA (p < 0.001), and OSI (p < 0.001) values were found to be significantly higher in AA patients than in the control group. The mean serum TAC value was significantly lower (p < 0.05) in cases than in controls. Significantly higher MDA (p < 0.001), TOC (p < 0.001), and OSI values (p < 0.001) and lower TAC values (p < 0.01) were found in severe AA than in mild or moderate AA. CONCLUSION: The demonstrated results confirmed the presence of oxidative stress and lipid peroxidation in AA. Whether these changes play a role in disease pathogenesis or result from the inflammatory process requires further investigation.