Mona Abdelrahim

Endogenous BTG2 expression stimulates migration of bladder cancer cells and correlates with poor clinical prognosis for bladder cancer patients.

Background:The B-cell translocation gene 2 (BTG2) is considered to act as a tumour-suppressor gene because of its antiproliferative and antimigratory activities. Higher levels of BTG2 expression in tumour cells have been linked to a better clinical outcome for several cancer entities. Here, we investigated the expression and function of BTG2 in bladder cancer.Methods:The expression of BTG2 in bladder cancer cells was silenced by RNA interference. Cell motility was investigated by wound healing and Boyden chamber assays. The protein expression of BTG2 in bladder cancer was studied by immunohistochemistry.Results:We observed that targeted suppression of BTG2 by RNA interference did not result in growth stimulation but led to a substantial inhibition of bladder cancer cell motility. Tissue microarray analyses of bladder cancer cystectomy specimens revealed that higher BTG2 expression levels within the tumours correlated strongly with a decreased cancer-specific survival for bladder cancer patients.Conclusion:These results indicate that endogenous BTG2 expression contributes to the migratory potential of bladder cancer cells. Moreover, high levels of BTG2 in bladder cancers are linked to decreased cancer-specific survival. These findings question the conception that BTG2 generally acts as a tumour suppressor and typically represents a favourable clinical marker for cancer patients.

Markers of inflammation and atherosclerosis in Egyptian patients with systemic lupus erythematosus

Background:  Cardiovascular events are markedly increased in systemic lupus erythematosus (SLE) and the mechanism of atherogenesis remains poorly understood. Low‐grade inflammation and endothelial dysfunction play pivotal roles in the initiation, progression and propagation of the atherosclerotic process. Several methods have been employed to assess endothelial function, among them the measurement of biomarkers of endothelial activation and dysfunction (intercellular adhesion molecule (ICAM)‐1). Since then, it has been reported that such biomarkers play a more important role than traditional risk factors in cardiovascular disease.

Quantitative Evaluation of Heavy Metals and Trace Elements in the Urinary Bladder: Comparison Between Cancerous, Adjacent Non-cancerous and Normal Cadaveric Tissue

The role of heavy metals and trace elements (HMTE) in the development of some cancers has been previously reported. Bladder carcinoma is a frequent malignancy of the urinary tract. The most common risk factors for bladder cancer are exposure to industrial carcinogens, cigarette smoking, gender, and possibly diet. The aim of this study was to evaluate HTME concentrations in the cancerous and adjacent non-cancerous tissues and compare them with those of normal cadaveric bladder. This prospective study included 102 paired samples of full-thickness cancer and adjacent non-cancerous bladder tissues of radical cystectomy (RC) specimens that were histologically proven as invasive bladder cancer (MIBC). We used 17 matched controls of non-malignant bladder tissue samples from cadavers. All samples were processed and evaluated for the concentration of 22 HMTE by using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). Outcome analysis was made by the Mann-Whitney U, chi-square, Kruskal-Wallis, and Wilcoxon signed ranks tests. When compared with cadaveric control or cancerous, the adjacent non-cancerous tissue had higher levels of six elements (arsenic, lead, selenium, strontium, zinc, and aluminum), and when compared with the control alone, it had a higher concentration of calcium, cadmium, chromium, potassium, magnesium, and nickel. The cancerous tissue had a higher concentration of cadmium, lead, chromium, calcium, potassium, phosphorous, magnesium, nickel, selenium, strontium, and zinc than cadaveric control. Boron level was higher in cadaveric control than cancerous and adjacent non-cancerous tissue. Cadmium level was higher in cancerous tissue with node-positive than node-negative cases. The high concentrations of cadmium, lead, chromium, nickel, and zinc, in the cancerous together with arsenic in the adjacent non-cancerous tissues of RC specimens suggest a pathogenic role of these elements in BC. However, further work-up is needed to support this conclusion by the application of these HMTE on BC cell lines.

Gene expression of excision repair cross-complementation group 1 enzyme as a novel predictive marker in patients receiving platinum-based chemotherapy in advanced bladder cancer

Background Excision repair cross-complementation group 1 enzyme (ERCC1) expression is most probably associated with cisplatin resistance in different tumors, including bladder tumors. Predictive role of ERCC1 expression in the neoadjuvant setting in bladder cancer had been studied as this genetic testing could personalize the chemotherapy by selecting the patients who would benefit from platinum-based chemotherapy. Participants and methods This is a descriptive study that was conducted on 80 patients with muscle invasive bladder cancer who received platinum-based chemotherapy. Clinical and histopathologic parameters along with immunohistochemical ERCC1 staining were examined and correlated with response rates and survival. Results The study showed a significant relationship between treatment response and ERCC1 expression of tumor tissue samples (P=0.013), indicating an association between negative immunoexpression and more favorable outcome. analysis of variance test revealed no significant difference neither between mean progression-free survival in different immunoexpression levels (P=0.794) nor mean overall survival in different immunoexpression levels (P=0.499). Conclusion Our study showed that there was a significant relationship between treatment response and ERCC1 expression of tumor tissue samples, although it did not show a significant difference between ERCC1 expression and mean overall survival or progression-free survival in different immunoexpression levels in patients with bladder cancer who received neoadjuvant platinum-based chemotherapy. ERCC1 may represent a potential predictive, but not prognostic, marker for platinum-based treatment in bladder cancer.

A woman with recurrent hematuria: a diagnostic challenge in Egypt

Objectives Thin basement membrane disease (TBMD) or benign familial hematuria is common in women. The median age is 37 years among adults. About two-third of the patients with TBMD have at least one other hematuric family member when five relatives are tested. Case report We hereby present a case of adult TBMD to clarify the clinicopathological characteristics of the disease in 56-year-old woman with long-standing intermittent dark colored urine with proteinuria, normal serum creatinine, and with normal blood pressure. Renal pathology showed normal renal tissue by using the light and immunofluorescence examination. Thinning of the glomerular basement membrane, ranging from 110 to 200 nm, was demonstrated by using electron microscopy. Conclusion Although it is part of routine nephropathology worldwide, electron microscopic examination of renal biopsies are rarely used in Egypt. This important diagnostic pillar should be more frequently used among our patients, especially when clinicopathologic diagnosis is unclear.

1754 DEVELOPMENT AND EXTERNAL VALIDATION OF LYMPH NODE DENSITY CUT-OFF AT RADICAL CYSTECTOMY: A MULTICENTRE STUDY

INTRODUCTION AND OBJECTIVES: To identify the prognostic role of lymph node density (LN-d) in a single series of patients undergone RC and to validate findings on an external series. METHODS: Between May 1998 and September 2009 data of 1084 Radical Cystectomies performed at two Institutes were collected in a prospectively-maintained database. After applying selection criteria (neither neoadjuvant nor adjuvant treatments, not salvage cystectomies) 979 out of 1084 patients (695 pN0 and 284 pN ) with non-metastatic bladder carcinoma were selected. The external validation of findings was performed on a single-centre series of 775 patients (590 pN0 and 185 pN ) with the same selection criteria. All patients underwent RC and pelvic lymphnode dissection (PLND). Once lymph node density (LN-d) and lymphnode count (LN-c) cut-off values were identified by maximally selected Log-rank analysis, the prognostic role of several variables on diseasefree survival (DFS) was assessed with univariable and multivariable Cox regression analyses. RESULTS: Statistically significant variables at univariable analysis were histological subtypes (p 0.001) [squamous cell carcinoma (SCC), urothelial carcinoma (UC), urothelial carcinoma with squamous differentiantion (US), adenocarcinoma (AC)], pT (p 0.001), pN (p 0.001), LN-d (p 0.001), PLND extent (p 0.001). At stepwise Cox regression analysis on the internal series of 979 patients pT (p 0.001), LN-d (p 0.001), extent of PLND (p 0.001) and histological subtypes (p 0.001) were independent predictors of DFS (Table 1). On the external cohort of 775 patients pT (p 0.001), LN-d (p 0.001) and histological subtypes (p 0.035) proved to have independent role on DFS (Table 1). CONCLUSIONS: LN-d thresholds identified in the internal cohort were independent predictor of DFS in the external validation cohort. LN-d, pT stage and histological subtypes were the only independent prognostic factors in both series.