Androgen Receptor Expression in Breast Carcinoma of Egyptian Patients.

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.

Neuro-folliculo-sebaceous cystic hamartoma is a unique entity.

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.

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

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

Immunolocalization of androgen receptor and estrogen receptors in skin tags.

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

Impact of fungal load on diagnosis and outcome of allergic fungal rhinosinusitis.

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.

Immunohistochemical dissimilarity between allergic fungal and nonfungal chronic rhinosinusitis.

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.

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.

Impact of E-cadherin expression pattern in melanocytic nevi and cutaneous malignant melanoma.

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.

The role of CK7, Ki-67, CD34 and vimentin in the differentiation between biliary atresia and idiopathic neonatal hepatitis in Egyptian cholestatic neonates.

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.

Diagnostic role of inhibin α-subunit and inhibin/activin ß-subunit in adrenal cortical and medullary tumors in Egyptian patients.

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.

The prognostic value of Skp2 expression in Egyptian diffuse large B-cell lymphoma.

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.

Is pyogenic ethmoidal osteitis the cause of complicated rhinosinusitis with subperiosteal orbital abscess?

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.

Immunohistochemical profile of ephrin A4 expression in human osteosarcoma.

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<0.05). The cytoplasmic pattern is the only staining pattern seen in metastatic cases, which may suggest its role in enhancement of invasion and metastasis. The differences in the distribution of the two patterns of ephrin A4 may indicate a different biological activity of this molecule depending on its localization. The nuclear localization of ephrin A4 requires further investigation to clarify the mechanism and the significance of the nuclear trafficking of ephrin A4.