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Cryptosporidium is one of the commonest opportunistic parasites. But, its chemotherapeuticoptions are limited, with controversy about the role of apoptosis in cryptosporidiosis. Caspasesare key molecules of apoptosis. The study assessed the role of apoptosis in cryptosporidiosisby studying the relationship between the effects of phenyl vinyl sulfone (PVS), nitazoxanide(NTZ) and combined therapy on Cryptosporidium parvum infection and caspase 3immunostaining. Ninety female laboratory bred Swiss Albino mice were divided into twomajor groups; immunocompetent and immunosuppressed. Both groups were divided into thefollowing subgroups, for each one respectively: negative control (1 & 6), infected control (2& 7), infected treated with PVS (3 & 8), infected treated with NTZ (4 & 9) and infected treatedcombined (5 & 10). Sacrification were done on 18th day post infection.Histopathological study of ileum was done and endogenous developmental stages werecounted. Also, caspase 3 immunohistochemical staining was carried out on ileal sections.Combined therapy in groups 5 &10 showed the highest reduction in mean number of endogenousdevelopmental stages as in G10 (P

Background: The discoidin domain receptor-1 (DDR1) is a non-integrin collagen receptor recently implicated in the collective cell migration of other cancer types. Objective: To review the immunohistochemical expression of discoidin domain receptor1 (DDR1) in non-neoplastic skin disease. Data Sources: A systematic search of MEDLINE (PubMed, Medscape, Science Direct. EMF-Portal) and internet was conducted on all articles published from 2002 to 2021. Study Selection: English-language reports of immunohistochemical expression of DDR1 on non-neoplastic skin disease. The initial search presented 90 articles where 30 studies had the inclusion criteria. Then, they were divided into 12 studies about immunopathogenesis of non-neoplastic skin disease, 9 studies about expression of discoidin domain receptor1 and 9 studies emphasized DDR1 expression in non-neoplastic skin disease. Data Extraction: Articles not reporting on immunohistochemical expression of DDR1 in non-neoplastic skin disease in the title or abstract were not included. 9 independent investigators extracted data on methods. Findings: Interaction of DDR1 with various receptors is important for the regulation of cell survival, migration, and differentiation in development and pathological conditions. The discovery of inhibitors of DDR1 kinase activity might be beneficial in several pathological conditions where DDR1 has been identified as a potential therapeutic target. Conclusion: Our review reported that the knowledge of the main cells and cytokines involved in the immunopathogenesis of non-neoplastic skin disease is essential for dermatologists to understand better the disease as well as the mechanism of action of the biologics, drugs that revolutionized the treatment of non-neoplastic skin disease in the last two decades.

Background: Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune blistering disease. PV autoantibodies disrupt desmosomal adhesion and cause acantholysis. Previous researches have shown that stem cells are indirectly involved as a result of desmoglein deficiency. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) as a follicular stem cell marker was evaluated in aim to correlate its intensity of expression with disease severity. Objective: To correlate LGR5 intensity of expression with disease severity. Patient and methods: This prospective cross sectional study was carried out on 20 PV patients. Patients were subjected to complete history taking, general, dermatological examination and assessment of disease severity by the Pemphigus Vulgaris Activity Score (PVAS), histopathological and immunohistochemical expression of LGR5 were done. Results: All studied cases showed positive cytoplasmic basal LGR5 expression in patchy manner. 75% of cases had mild intensity of expression, 15% had moderate intensity and their Histo (H) score ranged from 50-130 with Mean ±SD 110±18.92. There were no significant correlation between PVAS scores ''skin, mucosa and total involvement'' and H score of LGR5 expression. Conclusion: The current study could shed a new light on the disease and its correlation with stem cells, LGR5 as a stem cell marker could be related to the healing process in PV. However, it didn't correlate PVAS scores either in skin, mucosa or total involvement.

BACKGROUND Abnormal autophagy is known to be associated with the pathogenesis of some skin disorders. The protein Beclin1 plays a central role in the machinery of autophagy. AIM To assess the expression of Beclin1 in psoriasis, using immunohistochemical study in lesional and perilesional skin in patients with psoriasis, and to compare the results with those of an apparently healthy control (HC) group. METHODS This case-control study enrolled a total of 40 participants: 20 patients with chronic plaque psoriasis and 20 age- and sex-matched, apparently HCs. Skin biopsies were taken from (i) lesional and (ii) perilesional skin of patients with psoriasis and from (iii) normal skin of HCs for immunohistochemical evaluation of Beclin1 expression. RESULTS Epidermal Beclin1 expression was positive in all three studied groups. There was a significant difference between the three studied groups regarding Beclin1 epidermal topographic distribution, epidermal staining intensity, H score and H-score category (P

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers in Egypt with fatal outcome. The molecular pathogenesis of this type of cancer is so complex involving interaction of several signaling pathways. Among those is Wingless (WNT)/β-catenin signaling pathway, which is frequently activated in HCC. Objectives: To investigate the relationship of different localization patterns of β-catenin in relation to different histopathologic parameters in Egyptian HCC cases. Patients and methods: One hundred and twenty-one (121) HCC specimens were subjected for β-catenin evaluation by immunohistochemistry. Results: The studied HCC cases showed β-catenin membranous expression in 47/121 (38.8%) of cases, while nucleocytoplasmic localization was observed in 31/121 (25.6%). Most of HCC cases that showed single tumor mass presentation exhibited negative nucleocytoplasmic expression pattern (79.2%, P=0.02). Membranous pool of β-catenin was associated with adverse prognostic factors like increased positivity among high-grade cases (P=0.04), higher H score value in cases having lymphovascular invasion, positive lymph node and higher (advanced) TMN stages (P = 0.01, 0.00, 0.00 &0.03 respectively). Conclusion: HCC cases showed heterogeneous β-catenin expression pattern. Membranous β-catenin localization was associated with aggressive prognostic parameters of HCC.

Background: Psoriasis is a chronic, inflammatory immune mediated skin disease characterized by dense infiltrates of immunocytes especially macrophages. Cross talk between immunocytes and keratinocytes is thought to mediate the disease. Hparanase 2 inhibits activity of Heparanase 1 which is involved in this cross talk by degradation of heparin sulphate chains in the basement membrane and extra cellular matrix (ECM). Objective: To assess the of Heparanase2 in psoriasis through its immunohistochemical expression in lesional and perilesional skin of psoriasis patients. Patients and Methods: This prospective case control study was carried out on a total number of 60 subjects, they included 30 patients with chronic plaque psoriasis and 30 age and gender matched apparently normal subjects as control group. Skin biopsies were taken for immunohistochemical evaluation of Heparanase 2 expression. Results: Our results showed significant difference between lesional, perilesional and control groups regarding the status of epidermal Heparanase 2 expression (P = 0.038). All lesional epidermal expression was negative while perilesional epidermal expression was negative in 24 (80%) cases and positive in 6 (20%) cases, control epidermal expression was negative in 27 (90%) cases and positive in 3 (10%) cases. There was no significant difference between the three studied groups regarding dermal Heparanase 2 expression (P = 0.318). Conclusion: Downregulation of Heparanase 2 could be incriminated in the pathogenesis of psoriasis. Heparanase 2 could have a protective role in skin.

Background: Light chain3 is a sensitive autophagy-related protein distributed within the mammalian tissues. The role of LC3 localization in psoriasis pathogenesis is still poorly understood. Objective: This study aimed to investigate, for the first time up to our knowledge, the localization of Light chain3 (LC3) in the keratinocytes of psoriatic skin by immunohistochemical study. Materials and methods: This prospective case case-control study was carried out on 30 patients presented with chronic plaque psoriasis versus 30 age and gender-matched apparently healthy volunteers. Clinical data were collected and Psoriasis Area and Severity Index (PASI) was assessed. From all controls and cases (lesional and perilesional), skin biopsies were taken and the epidermis was assessed for histopathological changes and LC3 immunoreaction. Results: There was a highly significant difference (P

Purpose To evaluate the role of autophagy related gene 7 (ATG7) in non-melanoma skin cancer. Subjects and Methods This retrospective and prospective case-control study was performed on 104 patients with non-melanoma skin cancer (NMSC) in addition to 20 apparently healthy subjects matched for age and sex as a control group. Multiple skin biopsies were taken for immunohistochemical evaluation of ATG7 expression. Results Both epithelial and stromal ATG7 were expressed in all participants while all patients showed nucleocytoplasmic localization and controls showed both cytoplasmic and nucleocytoplasmic expression. In addition, significantly higher H-scores of ATG7 in both epithelium and stroma were detected in patients compared to controls (P

Autophagy dysregulation is involved in many diseases. The implication of autophagy in psoriasis pathogenesis is still uncertain. To investigate the role of Light Chain 3 (LC3), a good marker for autophagy, in psoriatic skin based on immunohistochemical study and correlate its expression - for the first time to the best of our knowledge - to clinicopathological data Prospective case-control study was conducted on 60 subjects (30 control, 30 psoriasis patients). Skin biopsies from control, lesional, and perilesional skin were processed for routine histopathological examination and LC3 immunoreaction assessment. There was a significant upregulation of the epidermal and dermal LC3 immunoreaction in the lesional skin compared with the control and perilesional skin specimens (

Background: Human JAKs are responsible for generating docking sites for human SSTAT phosphorylation. The role of JAKs in psoriasis pathogenesis has not been clearly explained. Aim: To investigate the role of JAK1 in psoriasis pathogenesis and to assess if this role is mediated through STAT3 or not, through evaluation of their immunohistochemical expression in the skin of psoriatic patients. Methods: This case-control study was carried out on 26 patients presenting with psoriasis vulgaris versus 26 age- and sex-matched apparently healthy volunteers. Psoriasis Area and Severity Index (PASI) scores were used to evaluate psoriasis severity. From all controls and cases (lesional and perilesional), skin biopsies were taken for histopathological and immunohistochemical JAK1 and STAT3 evaluation. Results: There was significant stepwise upregulation of JAK1 from controls to perilesional to lesional psoriatic skin of the patient group in both epidermis and dermis (P≤0.001 for both). Dermal JAK1 H-score was significantly associated with psoriasis severity (P=0.01). STAT3 was significantly overexpressed in lesional psoriatic skin over nonlesional skin (P

Background Vitiligo is an acquired autoimmune skin disorder. The often-visible lesions of vitiligo have a major impact on patients' quality of life and the results of the treatment regimens on offer are unsatisfactory, so there is a need for new therapeutic regimens. Recent advances in vitiligo pathogenesis have led to recognition of the importance of the JAK-STAT pathway as an attractive therapeutic option. Purpose To evaluate role of JAK1 and STAT3 in vitiligo. Methods This prospective case-control study was carried out on 35 patients presenting with vitiligo and 20 apparently healthy age- and sex-matched volunteers. Skin biopsies from controls and cases were taken for histopathological and immunohistochemical JAK1 and STAT3 evaluation. Results Epidermal and dermal overexpression of STAT3 was noted in lesional skin compared to the other groups (P=0.02 and P

Background Psoriasis is a common chronic recurrent immune-mediated disease of the skin. Liver X receptor-alpha (LXR-α) is a member of the nuclear receptor family of transcription factors. LXR-α was found to be expressed in the skin. Objective To assess immunohistochemical expression of LXR-α in psoriatic (perilesional and perilesional) skin compared with control and to correlate its expression with the clinical and histopathological parameters of that disease in the studied patients. Patients and methods This case–control study was carried out on 76 participants, including 38 patients having chronic plaque psoriasis, besides 38 age-matched and sex-matched apparently normal volunteers (control group). The severity of psoriasis was assessed by Psoriasis Area and Severity Index score. The skin biopsies were subjected to hematoxylin and eosin and immunohistochemical staining of LXR-α. Results There was a significant stepladder downregulation of LXR-α from control to perilesional psoriatic skin, ending with lesional psoriatic skin, regarding its expression and H score in epidermis and dermal elements (P

Carbonic anhydrase IX (CAIX) is an enzyme whose expression is very limited in normal tissues and it is highly expressed in various cancers. Therefore, inhibition of CAIX is considered as a promising therapeutic target for the treatment of solid tumors where hypoxic environment has developed. The aim of the current work is to evaluate the immunohistochemical (IHC) expression of CAIX in breast cancer (BC) of Egyptian patients and to investigate the associations of CAIX expression with the standard clinicopathologic features, IHC subtypes of BC, and overall survival. This retrospective study was conducted on 56 archival cases of Egyptian BC patients. Fifty-one of 56 cases (91.1%) showed positive expression of CAIX with cytoplasmic localization, whereas 5 cases (8.9%) showed negative expression. CAIX IHC overexpression is significantly associated with advanced stage and presence of coagulative tumor cell necrosis (P=0.03 and 0.02, respectively). Multivariate analysis revealed Ki67 labeling index and CAIX H-score grouping (P=0.03 and 0.02, respectively) as independent prognostic factors affecting BC patients' overall survival. We concluded that CAIX could play a role in the progression of the studied BC cases. CAIX is a good candidate for target therapy.

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

Aims Pleomorphic adenoma (PA) of the breast is a rare tumour seen usually in postmenopausal women. Although PA of the salivary glands (SG) is recognized to be a benign tumour, the nature and biology of similar tumours seen in the breast remains to be defined. The aim of this study was to describe PA of the breast that was reported on core biopsy as an invasive matrix-producing metaplastic breast carcinoma (MBC). Methods and results A core biopsy from a clinically malignant retroareolar mass showed mildly atypical polygonal cells with surrounding myxoid stroma. Immunohistochemistry showed expression of basal and luminal cytokeratins, but oestrogen receptor, human epidermal growth factor receptor 2 (HER2) and myoepithelial markers were negative. The excision specimen showed similar features, but in addition the stroma showed cartilage and bone. Also it was clear that the lesion was circumscribed and merged with a sclerosed papillary lesion consistent with what has been described as mammary PA. Conclusion This lesion shows an overlap of morphology and immunophenotype with SG-PA and with MBC. The majority of mammary PAs have a benign behaviour, but local recurrence and development of carcinoma occur. We propose a new terminology of pleomorphic adenoma-like tumour of the breast to reflect the uncertain nature of these tumours and help guide management decisions.

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.

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, ERβ, 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 ERβ 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 ERβ 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.

Background: Second to fourth digit (2D:4D) ratio is the ratio of index to ring fingers length. It reflects prenatal androgen exposure and sensitivity. Androgens are important in the pathogenesis of acne vulgaris, This ratio may therefore be of significance in determining the expression of androgen receptors. Aim: To investigate the relationship between second to fourth digit ratio and androgen receptor expression in female patients with acne vulgaris and to assess its association with clinical aspects of acne vulgaris. Methods: Females patients (n = 352) with different degrees of acne vulgaris severity and 168 age-matched females were enrolled. Right, left and total second to fourth digit ratios were calculated. Biopsies from all participants were processed for androgen receptor expression by immunohistochemical method. Results: Right, left and total second to fourth digit ratios were significantly lower in acne vulgaris patients than controls (P < 0.001 for all), and each of them had a significant negative correlation with duration of acne vulgaris (P < 0.001; P = 0.013; P < 0.001, respectively). Androgen receptors were detected in epidermal keratinocytes, hair follicles, sebaceous glands and fibroblasts. Right second to fourth digit ratio showed a negative correlation with androgen receptor H score of keratinocytes (r = −0.28;P = 0.02), hair follicles (r = −0.22; P = 0.05) and fibroblasts (r= −0.37;P = 0.001), while left second to fourth digit ratio demonstrated negative correlation with androgen receptor H score of sebocytes (r = −0.397; P < 0.000) only. Limitations: Lack of follow-up and absence of male participants were the main limitations of this study. Conclusion: A masculine second to fourth digit ratio in female patients could anticipate acne vulgaris development, its duration and severity. Moreover, this ratio is associated with an upregulation of cutaneous androgen receptors. Taken together, second to fourth digit ratio could help in designing plans for treatment of acne vulgaris.

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.

Fungal load colonization may modify the classic eosinophilic inflammation in allergic fungal rhinosinusitis (AFRS). We aimed to evaluate the impact of fungal load on diagnosis and outcome of AFRS. In the present cohort study fungal load differences were determined prospectively according to Gomori methenamine silver (GMS) fungal stained (histopathological and cytological examination) with the tenacious mucus, cheesy clay-like materials and sinus mucosa/polyps in 12 AFRS patients. Two groups with different fungal loads, AFRS with (six patients) and without (six patients) high fungal loads (HFL) were evaluated for nasal endoscopic score, paranasal sinuses CT score, histopathological and immunohistochemical changes. Endoscopic outcome scoring differences were evaluated for 1 year after endoscopic sinus surgery and 1 month oral corticosteroids treatment. No differences were observed between both groups (AFRS with/without HFL) concerning the total CT score and opacification features (P > 0.05). Eosinophils and CD3 + CD8 + T cell were dominant in both groups. More edema and less fibrosis were observed in HFL group. Gliotoxin producers Aspergilli were present in all HFL in comparison to 5/6 (83.3%) in cases without HFL. Fewer patients 1/6 (16.6%) and less number of recurrences/year 0.1 ± 0.4 occurred in the AFRS with HFL compared to the AFRS without HFL [5/6 (83.3%) and 1.16 ± 0.7) (P = 0.021 and 0.023, respectively]. In addition to mucus and mucosal tissues, cheesy clay-like materials must be assessed in AFRS cases. Although patients of AFRS with HFL had negligible clinical differences from ordinary AFRS without HFL, they had better outcome after treatment.

Introduction: Breast carcinoma (BC) is a heterogeneous disease, with distinctive molecular sub-types, influencing BC patients prognosis and therapeutic options. Androgen Receptor (AR) is a steroid nuclear receptor involved in complex signaling pathways, that are thought to play a role in cell proliferation. AR expression in relation to different molecular sub-types of BC is not clearly understood. Aim: The aim of this study was to evaluate the expression of AR in BC from Egyptian patients and correlate it with the standard clinico-pathologic variables, molecular sub-type of BC and the Overall Survival (OS). Materials and Methods: This retrospective study was conducted on 81 cases of BC from egyptian patients, stained immunohistochemically with AR. Chi-Square and KaplanMeier tests were applied to study the correlation between AR expression and clinicopathologic variables and the OS of BC patients respectively. Results: Among studied BC cases, 37.04% were immunoreactive to AR. AR immunoreactivity was significantly corrrelated with older age (p=0.03), post-menopausal status (p=0.001), lower grade (p=0.003), the presence of in-situ component (p= 0.014), early stage of presentation (p=0.03) and good-moderate NPI (0.009). It was also correlated with Positive ER, negative HER-2/neu, low Ki-67 proliferation index and luminal A subtype. AR expression didn’t correlate with the OS in the studied cases. Conclusion: AR was found to be related to favourable prognostic factors in BC but not to OS. It was particularly expressed in luminal A group and in significant proportion in Triple Negative Breast Carcinoma (TNBC), providing an opportunity for AR targeted therapy.

The differentiation between biliary atresia (BA) and idiopathic neonatal hepatitis (INH) is challenging with many histological overlaps especially in the first weeks of life. This study aimed to investigate the role of immunohistochemical staining of CK7, Ki67, CD34, and vimentin in addition to other clinicopathological features in the differentiation between BA and INH. Cases included 30 infants with BA and 30 infants with INH. The diagnosis was based on clinical, laboratory, and liver biopsy examination. Female gender and elevated serum gamma glutamyle transferase were in favor of BA. Portal tract changes, such as bile ductular proliferation documented by CK7, Ki67 immunostaining and angiogenesis documented by CD34 immunostaining, favored the diagnosis of BA. Copper associated protein was positive in 70% of BA cases, but not detected in INH cases. Parenchymatous changes, such as giant cell transformation and positive iron deposition and Kupffer cell proliferation documented by vimentin immunostaining, favored the diagnosis of INH.CK7, Ki67, CD34, and vimentin are helpful adjuvant immunostaining in the differentiation between BA and INH.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma worldwide. Both morphologically and prognostically, it represents a disease of a diverse spectrum. S-phase kinase-associated protein 2 (Skp2) is a member of mammalian F-box proteins, which displays S-phase-promoting function through ubiquitin-mediated proteolysis of the cyclin-dependent kinase inhibitor, p27. The aim of this study is to evaluate the prognostic value of Skp2 in DLBCL (70 cases) by immunohistochemical staining technique, and its correlation with the clinicopathological features and survival. Five (25%) control cases (reactive follicular hyperplasia) showed high Skp2 expression compared with 52.9% of DLBCL using 10% as a cutoff point with a significant difference (P=0.04). Skp2 was seen staining the large cells in proliferating germinal centers of the control group. High Skp2 expression in DLBCL was associated with several progressive parameters, such as advanced stage (P=0.036), involvement of more than one extranodal site (P=0.05), and high proliferation (P=0.0001). It was also significantly associated with the presence (P=0.007) and extent (P=0.002) of necrosis and inversely correlated with p27 expression (P=0.0001). From this study, Skp2 expression in DLBCL identified subset of cases characterized by aggressive features such as advanced stage, increased number of extranodal sites, high proliferation, and shorter survival time. The association of Skp2 with necrosis may be a reflection of its ability in promoting proliferative tumor capacity.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphomas worldwide. The pathogenesis of lymphomas is not yet well understood. SV40 induces malignant transformation by the large T-antigen (L-TAG) and promotes transformation by binding and inactivating p53 and pRb. L-TAG can bind pRb promoting the activation of the E2F1 transcription factor, thus inducing the expression of genes required for the entry to the S phase and leading to cell transformation. This immunohistochemical study was conducted to assess the prognostic role and relationship of SV40 L-TAG and E2F1 in diffuse large B-cell lymphoma (DLBCL) of Egyptian patients. This retrospective study was conducted on 105 tissue specimens including 20 follicular hyperplasia and 85 DLBCL cases. SV40 L-TAG was identified in 3/85 (4%) of DLBCL. High Ki-67 labeling index (Ki-67 LI) and apoptotic count were associated with high E2F1 expression (pfor all). No significant association was reached between E2F1 and SV40. E2F1 expression proved to be the most and first independent prognostic factor on overall survival of DLBCL patients (HR = 5.79, 95% CI = 2.3–14.6, andp). Upregulation of E2F1 has been implicated in oncogenesis, prognosis, and prediction of therapeutic response but is not seemingly to have a relationship with the accused SV40.

Objective The aim of this study was to evaluate the relationship between immunohistochemical (IHC) expression of carbonic anhydrase IX (CA IX) and the standard clinicopathological features of breast carcinoma (BC) in Egyptian patients. Background BC in Egyptian patients has specific features of a poor prognosis, such as higher stage at presentation and higher grade than that in developed countries. Hypoxia is present in most solid tumors and is associated with resistance to chemotherapy and radiotherapy as well as a more malignant phenotype. The CA IX level is elevated in response to hypoxia and is involved in tumor development and progression by regulating cellular activities, such as growth, survival, and adhesion. Patients and methods This retrospective study was carried out on 56 archival cases of Egyptian BC patients for the evaluation of IHC expression of CA IX. Results Fifty-one cases out of 56 (91.1%) showed positive expression of CA IX, whereas five (8.9%) cases showed negative expression. There were significant differences between CA IX IHC expression and tumor stage and stromal response (P = 0.03 and 0.002, respectively) as advanced stage and desmoplastic stroma in favor of overexpression. In terms of the CA IX staining pattern, 44 (78.5%) showed cytoplasmic localization and seven (12.5%) showed membranocytoplasmic localization. Moreover, there were significant differences between the CA IX cytoplasmic and the membranocytoplasmic pattern of positive cases in mitotic count (P = 0.04) as a high mitotic count is found more often in the cytoplasmic pattern. Conclusion Hypoxia (overexpression of CA IX) in BC of Egyptian patients is associated with poor prognostic parameters such as advanced stage and desmoplastic stromal response. The cytoplasmic pattern of CA IX expression in BC has been associated with mitotically active tumors. CA IX expression has no relationship with hormonal status, HER2/neu, Ki-67 LI, and IHC subtyping. Further large-scale studies are warranted to investigate the new opportunity for CA IX targeted therapies in BC.

Psoriasis (PsO) is T-cell-mediated disease resulting from aberrant activation of both innate and adaptive immunity. Perforin is a multi-domain, pore-forming protein. It is located within the cytoplasm of CD 8 cytotoxic T cells (CTLs) and natural killer cells (NK). The aim of this study was to evaluate the immunohistochemical (IHC) expression of perforin in lesional and perilesional skin of chronic plaque psoriatic patient and correlate its expression with the standard clinico-pathological variables. This prospective case-control study was conducted on 50 PsO patients and 30 age- and gender-matched healthy subjects as a control group. There were high-significant differences between lesional and perilesional skin of plaque PsO patients as regards to IHC perforin status and localization (p 0.001 for both). There was a high-significant difference between positive and negative perforin cases as regards to psoriasis area severity index (PASI) (p 0.000). There were significant differences between mild and moderate-to-severe intensity of IHC perforin expression as regards to triggering factors and PASI (p = 0.02 and 0.03, respectively). Localization of IHC perforin positive lymphocytes in both epidermis and dermis was significantly associated with higher degree of acanthosis and higher degree of inflammatory infiltrates in comparison with positive cells located in dermis (p = 0.001 for both). Perforin might have a putative signaling in early and late plaque PsO. Plaque psoriatic patients with positive perforin expression could be a candidate for a future target therapy to stop the proposed scenario and achieve a therapeutic response.

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.

Inhibin and activins are dimeric glycoproteins that are structurally and functionally related to transforming growth factor-β and are composed of 1 α-subunit and 1 of 2 β-subunits (βA or βB). In recent years, there has been controversy about their role in adrenal tumors and their suitability as a diagnostic/predictive marker. Inhibin α and inhibin/activin β protein expression was assessed on 47 adrenal tissue specimens by means of immunohistochemistry. Positive immunoreactivity of inhibin-α was seen in all studied hyperplastic adrenal glands, 90.9% of cortical adenomas, and 83.3% of adrenal cortical carcinomas. In contrast, the adrenomedullary neoplasms had a statistically significantly different behavior (P=0.001). We observed the negative expression of inhibin α in 85% and 80% of benign and malignant pheochromocytomas, respectively. As regards the immunoreactivity of inhibin/activin β, 80% of adrenal hyperplasias, 81.8% of cortical adenomas, and 83.3% of adrenal cortical carcinomas showed positivity. Strong-to-weak positive staining of inhibin/activin β was observed in 70% of benign pheochromocytomas, whereas malignant pheochromocytomas showed positive immunohistochemical staining in 40% of cases with weak intensity. The scoring of inhibin/activin β immunoreactivity between adrenocortical and adrenomeullary neoplasia failed to reach the significant value (P=0.1). Our results demonstrate that inhibin α had a diagnostic role, differentiating between the adrenocortical and adrenomedullary neoplasms. Moreover, inhibin/activin β might play a predictive role for malignant potential in pheochromocytoma. Further studies are warranted to determine whether they play a diagnostic/predictive role in adrenal tumors or are just surrogate markers for this group of neoplasia.

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.

Wilms tumor is a mixed embroynal neoplasm of the kidney . HER2 is an onco-protein. Its over-expression could be implicated in the development of many tumors. The clinico-demographic and pathological data of 28 Wilms tumor patients were , reviewed. The tissue samples were examined by light Microscopy then immunohistochemical staining for HER2/neu expression. Additional 28 normal surrounding renal tissue specimens were included. There was significant differences between HER2/neu positive and HER2/neu negative Wilms tumors in relation to stage, histological phase and epithelial differentiation (P > 0.05 for all). The overall survival advantage was noticed if Wilms tumor was at early stages (I and II) (Log-rank = 13.23 and P > 0.001), homologous epithelial differentiation (Log-rank = 6.01 and P = 0.04), as well as HER2/neu positive tumors (Log-rank = 6.14 and P = 0.013). A statistical significant trend toward a longer recurrence free survival was, noticed if Wilms tumor was at early stages (Log-rank = 21.22, P > 0.0000) and if HER2/neu positive (Log-rank = 8.53, P = 0.004). HER2/neu expression in Wilms tumor could be a marker for epithelial and homologous differentiation and its expression could be a good predictor for overall survival and longer recurrence free survival.

Ephrin receptors and ephrin ligands constitute one of the largest groups of tyrosine kinases. The division of ephrin receptors into type A or type B is determined by their ligand-binding specificities. Ephrin A4 as a ligand has a broad capacity to bind and stimulate different subtypes of ephrin A receptors. Little is known about the role of ephrins generally and ephrin A4 particularly in osteosarcoma. Ephrin A4 was immunohistochemically assessed on archival material from 46 primary osteosarcoma cases, 10 metastatic pulmonary lesions and 20 normal control bone specimens. Ephrin A4 was expressed in 100% of normal bone specimens, in 84.4% of primary osteosarcoma cases and in all metastatic pulmonary lesions. Cytoplasmic and nucleocytoplasmic patterns of ephrin A4 immunoreactivity were observed, with the predominance of the latter pattern in normal bone (100%), and in 43.5% of primary osteosarcoma cases, which showed a higher intensity of expression compared with normal bone (p

Caveolin-1 (CAV1) and caveolin 2 (CAV2) are the principal structural proteins of caveolae, sphingolipid and cholesterol-rich invaginations of the plasma membrane involved in vesicular trafficking and signal transduction. Over the recent years there has been controversy about their role in breast cancer and their suitability as markers of basal-like phenotype. Caveolin-1 and CAV2 protein expression was assessed on a tissue microarray containing 880 unselected invasive breast cancer cases, by means of immunohistochemistry. Caveolin-1 and CAV2 expression was observed in 13.4 and 5.9% of all breast cancer, respectively. Their expression was strongly associated with high histological grade, lack of steroid hormone receptor positivity (ER and PR), and expression of basal markers (basal cytokeratins, P63, P-cadherin). Furthermore, there was a significant association between CAV1 and CAV2 expression and basal-like phenotype. On univariate analysis only CAV2 had a prognostic impact on breast cancer-specific survival; however, this was not independent from other traditional markers on multivariate analysis. Our results demonstrate that both CAV1 and CAV2 are associated with basal-like phenotype. Further studies are warranted to determine whether they play an oncogenic role in basal-like/triple-negative breast cancer development or are just surrogate markers for this subgroup.

Objective The aim of the present study was to assess fibroproliferative healing after endoscopic sinus surgery (ESS) by endoscopic, histopathological, and immunohistochemical (IHC) examination. The secondary objectives were to assess the correlation between fibroproliferative tissue formation and the evaluated clinical parameters. Background Fibrous tissue formation is an inevitable process during wound healing after ESS that results in the formation of sinus adhesions and synechia and is reflected on patient's comfort and recovery from sinus diseases. Materials and methods Twenty chronic rhinosinusitis patients (12 with and eight without nasal polyposis) subjected to ESS were enrolled in the study. Patients were subjected to computed tomography and preoperative endoscopic staging of sinus disease. Patients were assessed at 2, 4, and 12 weeks postoperatively through endoscopic and tissue (histopathological and IHC) evaluation. Results There is a significant increase in the degree of fibroproliferation along the three visits in the form of fibroblast and myofibroblast proliferation (H&E stain) (P = 0.001 and P 0.05). Conclusion Wound healing after functional ESS along 12 weeks is associated with microscopic fibroproliferative healing, not apparent at macroscopic levels, and is proportional to preoperative computed tomography and endoscopic and operative technique staging.

Objectives The aim of this study was to explore the relationship between immunohistochemical expression of β-catenin and the relevant clinicopathological features of medulloblastoma in Egyptian patients. Background Medulloblastoma is a small round blue cell malignancy of the cerebellum and is a major cause of morbidity and mortality in pediatric oncology. Identification of the signaling pathways involved in the pathogenesis of medulloblastoma represents a key challenge for medulloblastoma management. The wingless (WNT)-signaling pathway has been reported to be responsible for 15% of sporadic medulloblastoma. β-Catenin represents the downstream effector of the WNT pathway. Activation of the WNT-signaling pathway results in stabilization of β-catenin and its translocation from the cytoplasm to the nucleus where it regulates the related genes. Patients and methods This retrospective study was conducted on 49 tissue specimens of medulloblastoma patients for evaluation of immunohistochemical expression of β-catenin. Results None of the studied medulloblastoma patients showed nuclear localization of β-catenin. However, 29 patients exhibited cytoplasmic staining and 20 patients were absolutely negative. No statistically significant difference was found when comparing patients with cytoplasmic β-catenin expression and negative patients with the studied parameters. In addition, the H-score value of patients with cytoplasmic β-catenin did not show significant relationship with the studied clinicopathologic parameters. Conclusion In view of the absence of nuclear localization of β-catenin, we could conclude that β-catenin does not play a role in the pathogenesis in all evaluated medulloblastoma patients. However, a large-scale study is recommended to elicit the exact role of the WNT-signaling pathway through dysregulation of components other than β-catenin.

Trichoepithelioma (TE) is a benign tumor of follicular origin that presents as small, skin-colored papules predominantly on the face. When more than one family member is affected, the disease is known as multiple familial trichoepithelioma (MFT). It is a rare autosomal dominant (AD) skin disease. Malignant transformation is very rare. We present a case of MFT in a female patient and her father with malignant transformation to basal cell carcinoma (BCC) in the father. We summarized the main histological differential parameters between TE and BCC and applied immunophenotyping for both by administration of Bcl2, CD34, CD10 and androgen receptor (AR) antibodies.