ABSTRACT
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.
Subject(s)
Axin Protein , Cicatrix, Hypertrophic , Keloid , Humans , Case-Control Studies , Cicatrix, Hypertrophic/pathology , Keloid/pathology , Prognosis , Stem Cells/metabolismSubject(s)
Lentigo/pathology , Neurofibromatoses/pathology , Adolescent , Biopsy, Needle , Diagnosis, Differential , Disease Progression , Female , Follow-Up Studies , Humans , Hyperpigmentation/diagnosis , Hyperpigmentation/etiology , Immunohistochemistry , Lentigo/diagnosis , Neurofibromatoses/diagnosis , Risk Assessment , Sampling Studies , Young AdultABSTRACT
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 Kaplan-Meier 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.
ABSTRACT
Folliculosebaceous cystic hamartoma (FSCH) is a distinct type of cutaneous hamartoma of pilosebaceous origin that usually occurs on the face. For FSCH, other parts have been reported such as the genital area, and the trunk. A 50-year-old woman presented with an asymptomatic dome-shaped scalp nodule. The clinical diagnosis was pilar cyst or tumor. Histopathological assessment showed FSCH with absolute neural component as the only mesenchymal stroma, leading to the diagnosis of folliculosebaceous cystic neural hamartoma. To the best of our knowledge, absolute neural stroma in FSCH has not been reported previously in the literature.
Subject(s)
Epidermal Cyst/pathology , Hair Follicle/pathology , Hamartoma/pathology , Mesenchymal Stem Cells/pathology , Neurons/pathology , Scalp/pathology , Sebaceous Glands/pathology , Biomarkers/analysis , Biopsy , Epidermal Cyst/chemistry , Epidermal Cyst/surgery , Female , Hair Follicle/chemistry , Hair Follicle/surgery , Hamartoma/chemistry , Hamartoma/surgery , Humans , Immunohistochemistry , Mesenchymal Stem Cells/chemistry , Middle Aged , Neurons/chemistry , Predictive Value of Tests , Scalp/chemistry , Scalp/surgery , Sebaceous Glands/chemistry , Sebaceous Glands/surgeryABSTRACT
Calcinosis cutis involves the inappropriate deposition of calcium within the dermis layer of the skin and is often associated with autoimmune diseases. A 3-year-old healthy Omani child presented for evaluation of asymptomatic hard nodule on the left upper eyelid. Pathological examination identified the mass as subepidermal calcified nodule. The patient had no history of trauma or metabolic disturbances. Serum levels of calcium and phosphate were normal. Idiopathic calcinosis cutis should be included in the differential diagnosis for eye lid mass.
ABSTRACT
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.
Subject(s)
Cyclooxygenase 2/biosynthesis , NF-kappa B/biosynthesis , Psoriasis/metabolism , Adult , Case-Control Studies , Female , Humans , Immunohistochemistry , Male , Psoriasis/pathology , Up-RegulationABSTRACT
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.
Subject(s)
Killer Cells, Natural/metabolism , Perforin/metabolism , Psoriasis/metabolism , Skin/metabolism , T-Lymphocytes, Cytotoxic/metabolism , Adult , Aged , Case-Control Studies , Female , Humans , Immunohistochemistry/methods , Male , Middle Aged , Prospective StudiesABSTRACT
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.
Subject(s)
Carcinoma, Basal Cell/metabolism , Carcinoma, Squamous Cell/metabolism , Glioma/metabolism , Skin Neoplasms/metabolism , Transcription Factors/metabolism , Adult , Aged , Aged, 80 and over , Carcinoma, Basal Cell/diagnosis , Carcinoma, Basal Cell/pathology , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , Female , Glioma/diagnosis , Glioma/pathology , Humans , Male , Melanoma/metabolism , Middle Aged , Skin/metabolism , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Zinc Finger Protein GLI1ABSTRACT
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.
Subject(s)
Acne Vulgaris , Propionibacterium acnes , Toll-Like Receptor 2/immunology , Toll-Like Receptor 2/metabolism , Acne Vulgaris/immunology , Acne Vulgaris/microbiology , Acne Vulgaris/pathology , Adolescent , Adult , Dermis/immunology , Dermis/metabolism , Dermis/pathology , Epidermis/immunology , Epidermis/metabolism , Epidermis/pathology , Female , Gram-Positive Bacterial Infections/immunology , Gram-Positive Bacterial Infections/metabolism , Gram-Positive Bacterial Infections/pathology , Humans , Immunohistochemistry , Male , Young AdultABSTRACT
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.
Subject(s)
Mast Cells/pathology , Receptors, Androgen/metabolism , Receptors, Estrogen/metabolism , Skin/metabolism , Adult , Female , Fibroblasts/metabolism , Humans , Immunohistochemistry , Male , Middle AgedABSTRACT
BACKGROUND: Lipoid proteinosis (Urbach-Wiethe disease) is a rare progressive autosomal recessive disorder, characterized histologically by deposition of periodic acid Schiff-positive, diastase resistant, hyaline-like material into the skin, upper aerodigestive tract, and internal organs. MAIN OBSERVATION: We report two cases of lipoid proteinosis. A 2-year-old girl presented with vesiculobullous skin lesions on her face, trunk, extremities and scalp, inability to protrude the tongue and hoarseness of voice that appeared few months after birth. The other case is a 4-year-old girl, who presented with waxy papules on face and trunk, hoarseness of voice and enlarged lips and tongue. The lesions healed leaving pitted scars in both cases. Based on clinical, histopathological and laryngoscopy findings, lipoid proteinosis was diagnosed in both cases. Acitretin was started in a dose of 0.5 mg/kg/day in every child. Complete remission of cutaneous lesions and improvement of the hoarseness was observed after one year. CONCLUSION: Acitretin may be benificial for treatment of mucosal and cutaneous lesions in lipoid proteinosis.
ABSTRACT
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.
Subject(s)
Rhinitis, Allergic, Perennial/diagnosis , Rhinitis, Allergic, Perennial/microbiology , Sinusitis/diagnosis , Sinusitis/microbiology , Adult , Cohort Studies , Female , Humans , Immunohistochemistry , Male , Nasal Polyps/diagnosis , Nasal Polyps/microbiology , Nasal Polyps/surgery , Prospective Studies , Recurrence , Rhinitis, Allergic, Perennial/pathology , Rhinitis, Allergic, Perennial/surgery , Sinusitis/pathology , Sinusitis/surgery , Sphenoid Sinus/diagnostic imaging , Tomography, X-Ray Computed , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE: To investigate the role of inducible nitric oxide synthases (iNOS) and nuclear factor-kappa B (NF-κB) in the pathogenesis of melasma through their immunohistochemical (IHC) co-localization in skin of melasma and to correlate their expression with the clinical and the histopathological data. STUDY DESIGN: This prospective case-control study was conducted on 34 female patients with melasma and 30 age- and gender-matched healthy subjects as a control group for evaluation of IHC expression of iNOS and NF-κB in melasma. RESULTS: There were significant differences between lesional and perilesional skin regarding iNOS intensity, iNOS histo-score (H-score), NF-κB intensity, and NF-κB H-score (p < 0.001 for all). There were significant associations between the higher values of H-scores for both iNOS and NF-κB and positive family history (p = 0.002 and p = 0.001, respectively) and very severe melasma areas and severity index score (p < 0.001 and p = 0.001, respectively). There was a positive correlation between H-score values of both iNOS and NF-κB (r = +0.604 and p < 0.001). CONCLUSION: The IHC co-localization and direct correlation of both iNOS and NF-κB in melasma could provide evidence about their role as co-players in melanogenesis and might provide new targets for a more efficient treatment for melasma.
Subject(s)
Melanosis/genetics , NF-kappa B/biosynthesis , Nitric Oxide Synthase Type II/biosynthesis , Adult , Case-Control Studies , Female , Gene Expression Regulation , Humans , Melanosis/pathology , Nitric Oxide Synthase Type II/geneticsABSTRACT
BACKGROUNDS: Diagnosis of allergic fungal rhinosinusitis (AFRS) is complicated because of the presence of fungi on mucosal surfaces of sinonasal passages. The objectives of this study were to define, using immunohistochemistry, lymphocyte populations associated with noninvasive fungal-related chronic rhinosinusitis (CRS; AFRS and FBs [FB]) relative to CRS with nasal polyposis (CRSwNP) and CRS without nasal polyposis (CRSsNP) as a means of diagnosing different forms of CRS. METHODS: Sinus CT scans, nasal endoscopy scores, and the presence of eosinophilic fungal mucin or FBs were used to prospectively define patient groups with CRS who had failed medical treatment and were undergoing endoscopic sinus surgery. Four patient groups were identified: AFRS, FB, CRSwNP, and CRSsNP. Tissue specimens were studied and graded for histopathological changes. Immunophenotyping of mucosal lymphocytes was performed using anti-CD3, -CD20, -CD4, -CD8, -CD56, and -perforin antibodies. RESULTS: Nasal polyposis scores were similar between AFRS and CRSwNP. Radiological changes associated with AFRS can also be present in CRSwNP, e.g., heterogenicity in 9/30 (30%), expansion in 25/30 (83%), and bony attenuation of the ethmoid trabeculae in 19/30 (63%). Different grades of basement membrane thickness, edema, and fibrosis were observed. In both types of noninvasive fungal rhinosinusitis, CD3+ T lymphocytes were most commonly identified. In cases of AFRS, most T cells were CD8+ (p < 0.001). In FB cases, CD4+ lymphocytes were dominant (p < 0.001). In nonfungal CRS cases, CD20+ lymphocytes (B lymphocytes) predominated (p < 0.001). CONCLUSION: Although CT scans and histological examination can assist the diagnosis of rhinosinusitis, tissue immunophenotyping can be used in defining different types of fungal and nonfungal CRS cases.
Subject(s)
Antigens, CD/immunology , Immunohistochemistry , Mitosporic Fungi , Mycoses/diagnosis , Nasal Polyps/diagnosis , Rhinitis/diagnosis , Sinusitis/diagnosis , Adult , Antigens, CD20/immunology , Biomarkers/metabolism , CD3 Complex/immunology , CD4 Antigens/immunology , CD56 Antigen/immunology , CD8 Antigens/immunology , Chronic Disease , Cytotoxins/immunology , Diagnosis, Differential , Eosinophils/immunology , Female , Humans , Immunohistochemistry/methods , Immunophenotyping/methods , Male , Middle Aged , Mitosporic Fungi/isolation & purification , Mycoses/complications , Mycoses/immunology , Mycoses/therapy , Nasal Polyps/immunology , Nasal Polyps/microbiology , Nasal Polyps/therapy , Perforin/immunology , Prospective Studies , Rhinitis/immunology , Rhinitis/microbiology , Rhinitis/therapy , Rhinitis, Allergic , Rhinitis, Allergic, Perennial/diagnosis , Sinusitis/immunology , Sinusitis/microbiology , Sinusitis/therapyABSTRACT
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.
Subject(s)
Carcinoma/genetics , Gene Expression Regulation, Neoplastic , Neoplasm Recurrence, Local/genetics , Neoplastic Stem Cells/metabolism , Octamer Transcription Factor-3/genetics , Receptor, Notch1/genetics , Stromal Cells/metabolism , Urinary Bladder Neoplasms/genetics , Adult , Aged , Carcinoma/metabolism , Carcinoma/pathology , Cell Differentiation , Cell Proliferation , Cystitis/genetics , Cystitis/metabolism , Cystitis/pathology , Female , Humans , Immunohistochemistry , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Neoplastic Stem Cells/pathology , Octamer Transcription Factor-3/metabolism , Receptor, Notch1/metabolism , Signal Transduction , Stromal Cells/pathology , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathologyABSTRACT
OBJECTIVE: To explore the relationship between the immunohistochemical expression of E-cadherin and the relevant clinicopathologic features in various types of melanocytic nevi and cutaneous malignant melanoma (CMM). STUDY DESIGN: Using standard immunohistochemical techniques, we examined 30 CMMs, 30 melanocytic nevi and 10 sex- and age-matched volunteers for the expression of E-cadherin. RESULTS: A total of 90% of melanocytic nevi and all dysplastic nevi showed positive cytoplasmic immunoreactivity for E-cadherin with decreased intensity at the deeply located cells. A significant difference was noticed between types of CMM regarding the pattern of immunostaining of E-cadherin (p < 0.01), whereas all nodular malignant melanomas (NMMs) express the membranous pattern in contrast to the cytoplasmic one in other types of CMM. Reduced overall survival was significantly associated with advanced stage, late Clark level and membranous pattern of E-cadherin expression. CONCLUSION: E-cadherin expression in nevi is related to the degree of melanocytic maturation. Qualitative changes in the expression and cellular localization of E-cadherin are observed in melanoma that may reflect different stages of progression with molecular changes and may imply a prognostic marker.
Subject(s)
Cadherins/biosynthesis , Melanoma/metabolism , Nevus, Pigmented/metabolism , Skin Neoplasms/metabolism , Adult , Aged , Cadherins/analysis , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Melanoma/mortality , Melanoma/pathology , Middle Aged , Nevus, Pigmented/mortality , Nevus, Pigmented/pathology , Proportional Hazards Models , Retrospective Studies , Skin Neoplasms/mortality , Skin Neoplasms/pathologyABSTRACT
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.
Subject(s)
Biliary Atresia/diagnosis , Jaundice, Neonatal/diagnosis , Biliary Atresia/metabolism , Biliary Atresia/pathology , Diagnosis, Differential , Egypt , Female , Humans , Immunohistochemistry/methods , Infant , Infant, Newborn , Jaundice, Neonatal/metabolism , Jaundice, Neonatal/pathology , Keratin-7/metabolism , Ki-67 Antigen/metabolism , Male , Receptors, IgG/metabolism , Retrospective Studies , Vimentin/metabolismABSTRACT
Inhibin and activins are dimeric glycoproteins that are structurally and functionally related to transforming growth factor-ß and are composed of 1 α-subunit and 1 of 2 ß-subunits (ßA or ßB). 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 ß 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 ß, 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 ß 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 ß 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 ß 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.
Subject(s)
Adrenal Gland Neoplasms/diagnosis , Adrenocortical Adenoma/diagnosis , Adrenocortical Carcinoma/diagnosis , Biomarkers, Tumor/metabolism , Brain Stem Neoplasms/diagnosis , Inhibin-beta Subunits/metabolism , Inhibins/metabolism , Pheochromocytoma/diagnosis , Adrenal Gland Neoplasms/metabolism , Adrenocortical Adenoma/metabolism , Adrenocortical Carcinoma/metabolism , Adult , Aged , Brain Stem Neoplasms/metabolism , Diagnosis, Differential , Female , Humans , Immunohistochemistry , Male , Middle Aged , Pheochromocytoma/metabolism , Prognosis , Sensitivity and SpecificityABSTRACT
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.
Subject(s)
Cell Proliferation , Gene Expression Regulation, Neoplastic , Lymphoma, Large B-Cell, Diffuse/metabolism , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/pathology , S-Phase Kinase-Associated Proteins/biosynthesis , Adolescent , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Egypt , Female , Humans , Immunohistochemistry , Male , Middle Aged , Survival RateABSTRACT
Multiple theories were described concerning the pathogenesis of orbital infection in rhinosinusitis, but no theory was proved. Understanding the cause of complication can allow its proper management. We speculate that subperiosteal orbital abscess (SPOA) secondary to rhinosinusitis is similar to subperiosteal abscess associated with osteomyelitis of bone all over the body. The objective was to evaluate bony changes of the ethmoidal sinuses in complicated rhinosinusitis patients with SPOA. This prospective controlled study was performed on eight patients undergoing endoscopic sinus surgery drainage for rhinosinusitis complicated with SPOA. Age, radiographic bony characteristics, and histopathological findings were all documented. Ethmoidal bone specimens were examined and assessed histopathologically. Purulence of SPOA was collected and sent for cultures. The authors evaluated normal ethmoidal bone specimens taken endoscopically from the medial wall of obstructing concha bullosa in ten control patients. The analysis revealed CT and histopathologic changes consistent with high grades of ethmoidal bone pyogenic osteitic changes. Coagulase-positive staphylococci were the predominant cultured bacteria (62.5%) in SPOA. These findings suggest that orbital subperiosteal abscess in rhinosinusitis patients is attributed to diffuse higher grades of ethmoidal sinus bony pyogenic osteitis. Staphylococcus aureus is the most commonly involved cultured bacteria. Bony osteitis in rhinosinusitis patients with SPOA is similar clinically and histopathologically in its character and behavior to osteomyelitis of bone all over the body with associated subperiosteal abscess.