Asmaa Gaber Abdou

Helicobacter pylori infection in patients with chronic urticaria: correlation with pathologic findings in gastric biopsies

Background  Chronic urticaria is a persistent urticaria lasting longer than 6 weeks, affecting 20% of the general population. Various infectious agents have been reported as causes of urticaria, including Helicobacter pylori, which is a common worldwide bacterial infection. Its role in inducing allergic conditions, such as chronic urticaria, has been suggested in some reports and ignored in others.

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.

Ephrin A4 expression in osteosarcoma, impact on prognosis, and patient outcome

BACKGROUND Ephrin A4 is one of the ephrin ligand molecules belonging to the tyrosine kinases receptor family. It was originally identified in a T-lymphoma cell line and seen to be expressed in human adult tissue as well as several tumor types. In our previous study, we showed the unique pattern of ephrin A4 immunohistochemical staining, which differed according to the type of examined bone specimens (normal bone, primary, and metastatic osteosarcoma lesions). The aim of the present study is to evaluate the prognostic impact of ephrin A4 expression in a group of primary osteosarcoma patients. MATERIALS AND METHODS Ephrin A4 immunohistochemical expression was carried out on 47 primary osteosarcoma cases. RESULTS Ephrin A4 was expressed in 82.9% of osteosarcoma cases with cytoplasmic localization in 58.9% of positive cases. The cytoplasmic pattern was significantly associated with aggressive histopathological types of osteosarcoma (P = 0.02), advanced stage (P = 0.04), the presence of metastasis (P = 0.03), inferior response to neoadjuvent chemotherapy (P = 0.04), and tended to be associated with a shorter event-free survival (P = 0.09). CONCLUSIONS The cytoplasmic pattern of ephrin A4 could identify a subgroup of primary osteosarcoma patients with a high liability for progression, poor prognosis, and inferior response to chemotherapy.

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.

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 analysis of the role and relationship between Notch-1 and Oct-4 expression in urinary bladder carcinoma

Most tumors contain a minor population of cancer stem cells that are responsible for tumor heterogeneity, resistance to therapy and recurrence. Oct‐4 is a transcription factor responsible for self‐renewal of stem cells, whereas the Notch family of receptors and ligands may play a pivotal role in the regulation of stem cell maintenance and differentiation. This study aimed at an evaluation of Oct‐4 and Notch‐1 expression in both carcinoma and stromal cells of 83 cases of primary bladder carcinoma and to study the relationship between them. Notch‐1 was expressed in carcinoma and stromal cells of all malignant cases, where expression in both cell types was correlated with parameters indicating differentiation, such as low grade (p < 0.05) and less proliferation (p < 0.05). However, Notch‐1 expression in stromal cells was associated with nodal metastasis (p = 0.016) and advanced stage (p = 0.030). 56.6 and 75.9% of carcinoma and stromal cells of malignant cases showed Oct‐4 expression, respectively. Oct‐4 expression in carcinoma cells or stromal cells was associated with aggressive features of bladder carcinoma, such as poor differentiation (p = 0.001), high proliferation (p < 0.001, 0.030), and liability for recurrence (p = 0.010, p < 0.001). There was an inverse relationship between Notch‐1 and Oct‐4 expression in carcinoma cells (p = 0.002), but stromal expression of Notch‐1 was found to be associated with a nuclear pattern of Oct‐4 expression in carcinoma cells (p = 0.030). Oct‐4 as a stem cell marker is expressed in carcinoma cells and in stromal cells of bladder carcinoma, where they may cooperate in the progression of bladder carcinoma by acquiring aggressive features, such as a liability for recurrence and dissemination. Notch‐1 is also expressed in both carcinoma cells and stromal cells of bladder carcinoma. Although they could share in enhancing differentiation, stromal expression of Notch‐1 may have a bad impact, possibly through up‐regulation of the active nuclear form of Oct‐4 in carcinoma cells.

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.

GLUT-1 Expression in Cutaneous Basal and Squamous Cell Carcinomas

Glucose uptake is a key regulating step in glucose metabolism and is mediated by facilitative glucose transporters (GLUTs), and GLUT-1 is the predominant glucose transporter in many types of human cells. Cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) represent the most common skin cancer in Egypt. The present study aimed at evaluation of the pattern and distribution of GLUT-1 in cutaneous BCC (16 cases) and SCC (16 cases) by means of immunohistochemistry. GLUT-1 was expressed in all SCC (100%) and in 62.5% of BCC. Membranous pattern of GLUT-1 was seen in 62.5% of SCC and 31.25% of BCC. Positivity (P = .02) and percentage (P = .000) of GLUT-1 expression were in favor of SCC in comparison to BCC. The high percentage of GLUT-1 expression was associated with high grade in SCC (P = .03). The immunoreactivity for GLUT-1 was more in the periphery of malignant nests of SCC while it was more in the center of BCC nests. GLUT-1 is overexpressed in cutaneous non–melanoma skin cancer. Its expression in SCC is related to differentiation status, and its expression in BCC is intimately associated with squamous metaplastic areas.

Assessment of Cryptosporidium parvum infection in immunocompetent and immunocompromised mice and its role in triggering intestinal dysplasia

OBJECTIVES There is an association between chronic inflammation and cancer, including colon cancer. Cryptosporidium parvum is a protozoan parasite that infects the gastrointestinal epithelial cells causing several parasitological and pathological changes. It is incriminated in the development of colorectal cancer in immunosuppressed individuals. Cyclin D1 expression is essential for cell cycle progression and its overexpression has been reported in colorectal cancer. This work aimed to study the gastrointestinal changes, including parasitological and pathological changes, induced by C. parvum infection in both immunocompetent and in chemically immunosuppressed mice, together with immunohistochemical assessment of cyclin D1 expression in infected tissues. In addition, the effectiveness of nitazoxanide (NTZ) in the treatment of cryptosporidiosis was evaluated. METHODS This study included six groups of mice: group I, infected; group II, infected and immunosuppressed; group III, infected and treated with NTZ; group IV, infected, immunosuppressed, and treated with NTZ; and groups V and VI representing non-infected controls. Mice were subjected to stool examination for oocyst counts and were later sacrificed for intestinal dissection and routine histopathological examination of pathological changes; the endogenous developmental stages of the parasite were counted and immunohistochemical staining was carried out for the determination of cyclin D1. RESULTS Group II showed the highest numbers of oocysts shed and endogenous developmental stages compared to the other groups. Intestinal dysplastic changes were seen only in groups I and II, where these changes were in favor of group II compared to group I. High-grade dysplasia was seen in four out of 20 mice in group II and was significantly associated with the number of endogenous developmental stages of C. parvum. NTZ was effective in the treatment of Cryptosporidium infection, with a greater effect in group III than in group IV. CONCLUSIONS C. parvum is one of the infectious agents that may induce intestinal dysplasia, including the high-grade category, which occurs particularly in the presence of immune suppression states and elevated endogenous parasite loads. Cyclin D1 is a good and useful marker for the detection of intestinal dysplasia. The effectiveness of NTZ is dependent on the immune status of the infected host.

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.