Rehab Monir Samaka

Caveolin 1 and Caveolin 2 are associated with breast cancer basal-like and triple-negative immunophenotype

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.

Two Egyptian cases of lipoid proteinosis successfully treated with acitretin

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.

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.

HER2/neu Expression: A Predictor for Differentiation and Survival in Children With Wilms Tumor

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.

Does JC virus have a role in the etiology and prognosis of Egyptian colorectal carcinoma

John Cunningham virus (JCV) encodes an oncogenic T‐antigen, which is capable of interacting with key growth regulatory pathways. JCV definite role as causal agent of human cancer, still awaits final confirmation. The present study was conducted to assess the possible role of JCV in Egyptian colorectal carcinoma (CRC) and correlate the expression with the clinicopathological features and survival. JCV in situ hybridization (ISH) signals and large T antigen immunoreactivity were examined in 87 colonic specimens. Positive glandular JCV ISH signals were detected in 20%, 25% and 40% of normal, adenoma and CRC cases respectively. Stromal JCV ISH signals were identified in 26% of CRC cases and 5% of adenoma however, normal mucosa did not show stromal positivity with significant difference (p = 0.03). Glandular JCV expression was significantly associated with high grade (p = 0.03), high mitotic index (p=0.02) and low apoptotic index (p = 0.00). Positive stromal signals were significantly associated with low apoptosis (p = 0.00). No positive nuclear immunostaining of JCV large T antigen was detected in all specimens. JCV stromal expression was the 2nd most powerful indicator of short survival and bad prognosis (p = 0.03) in CRC patients. JCV might play an etiological role in CRC tumorogenesis and short survival in Egyptian CRC patients.

Multiple familial trichoepithelioma with malignant transformation

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.

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.

Pleomorphic adenoma-like tumour of the breast

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).

Immunohistochemical Evaluation of Leptin Expression in Wound Healing: A Clue to Exuberant Scar Formation.

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<0.001 for both) and dermis (P<0.001 for both) and to surgical scars both in epidermis (P=0.0006, P=0.01, respectively) and dermis (P=0.0001, P=0.001, respectively). Higher leptin H score was significantly associated with older age (P=0.02) and positive family history (P=0.002) in keloid cases and with axial site in keloid and HS cases (P=0.001, P=0.02, respectively). Significant positive correlation was noted between epidermal and dermal leptin H scores in keloids (r=+0.37, P=0.04) and HS (r=+0.39, P=0.02). This may be due to epithelial-mesenchymal interactions in scar pathogenesis. In conclusion, in situ leptin overexpression may increase the possibility of keloid and HS occurrence through altered cytokine production and prolonged healing phases with excessive deposition and delayed collagen degradation. This may open an avenue for research for new therapeutic modalities based on its inhibition.

Nuclear Factor Kappa B and Cyclo-Oxygenase-2: Two Concordant Players in Psoriasis Pathogenesis

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.