Gastric Carcinoma with low ROR alpha, low E- Cadherin and High LAPTM4B Immunohistochemical Profile; is associated with unfavorable prognosis in Egyptian patients.

In view of multiplicity of carcinogenic pathways of gastric carcinoma (GC), poor survival and chemotherapy resistance, more analysis of these pathways is required for prediction of prognosis and developing new therapeutic targets. Knocking down of RORα; induces tumor cell proliferation and epithelial-mesenchymal transition (EMT). LAPTM4B has been suggested to be associated with EMT which promote tumor invasion. This work aimed to investigate prognostic role of RORα, LAPTM4B, and E-Cadherin expression in GC. This retrospective immunohistochemical study assesses the expression of RORα, LAPTM4B, and E-Cadherin in 73 primary gastric carcinomas. Low RORα and high LAPTM4B expression in GC cases were associated with unfavorable prognostic factors such as positive lymph nodes, and high tumor budding. E-Cadherin heterogeneous staining was associated with poor prognostic criteria, such as diffuse type GC and high tumor budding. Low RORα, high LAPTM4B, and heterogeneous E-Cadherin were the most common immunohistochemical profile in GC cases. Low RORα expression showed poor prognostic impact on overall patient survival. In conclusion, RORα and LAPTM4B may have crucial role in GC aggressiveness. The predominance of low RORα, high LAPTM4B, and heterogeneous or negative E-Cadherin immunohistochemical profile in GC cases with unfavorable pathological parameters suggested that this profile may predict tumor behavior.

ROC-1, P21 and CAIX as markers of tumor aggressiveness in bladder carcinoma in Egyptian patients.

BACKGROUND: Bladder cancer (BC) is one of the most common malignancies in Egypt, representing about 8.7% of cancers in both sexes with more predominance in males, making identification of valuable predictive and prognostic markers, mandatory. Cullin-RING ligases (CRL) play an important role in the ubiquitination of cell cycle-related proteins or other proteins (e.g., DNA replication protein, signal transduction protein). Regulator of Cullins-1 (ROC-1) is a key subunit of CRL. P21 belongs to the family of cyclin dependent kinase inhibitors (CKIs) which regulates cell cycle by inactivating Cyclin- Dependent Kinases key regulators of the cell cycle. CAIX a highly active member of the family of carbonic anhydrases has gained much interest as a hypoxic marker. Hypoxia is a consequence of the rapid growth of many tumors, including bladder cancer, and is an important regulator of gene expression and resistance to chemotherapy and radiotherapy. Therefore the purpose of this study is to evaluate the role of ROC-1, CAIX and P21 and its relationship with the clinico-pathological features of bladder cancer in Egyptian patients. METHODS: Using the standard immunohistochemical technique, ROC-1, CAIX and P21 expression in 80 primary bladder carcinomas and 15 normal bladder specimens as control group were assessed. The bladder carcinoma cases included 50 cases with muscle invasive bladder cancer and 30 cases with non-muscle invasive bladder cancer. RESULTS: Over expression of ROC-1, CAIX and P21 in BC were significantly associated with muscularis propria invasion and high grade BC. ROC-1, CAIX and P21, showed significant inverse relationship in primary BC cases. CAIX expression was significantly higher in BC compared with controls. Regarding the survival analysis, expression of ROC-1, CAIX and P21 didn't affect the survival of BC patients. CONCLUSIONS: High expression of ROC-1, CAIX and P21 could be promising potential biomarkers for identifying patients with poor prognostic factors in bladder cancer serving as potential targets for cancer therapy.

Aquaporin 3 and E-Cadherin Expression in Perilesional Vitiligo Skin.

INTRODUCTION: Vitiligo is a common dermatologic disorder with debated aetiology. Most studies focused on role of melanocytes and few investigated the role of keratinocytes in pathogenesis of the disease. AIM: To investigate the keratinocyte adhesion in perilesional vitiligo skin through the immunolocalization of Aquaporin-3 (AQP3) and E-cadherin. SETTING AND DESIGN: Sixty five subjects were selected. These included 40 cases with vitiligo and 25 age and gender-matched healthy subjects as a control group. MATERIALS AND METHODS: Skin biopsies were taken from perilesional skin of cases and from site-matched areas of control subjects. The expression of AQP3 and E-cadherin was evaluated by immunohistochemical techniques. STATISTICAL ANALYSIS: Results were statistically analysed using IBM personal computer and the statistical package SPSS version 11. Fisher-exact and Chi-square tests were used to study the association between two qualitative variables. Mann-Whitney test was used for comparison between quantitative variables not normally distributed. Spearman's correlation coefficient was used to assess correlation between two quantitative variables. The p≤0.05 was considered significant. RESULTS: Regarding AQP3 expression, strong intensity, diffuse distribution, higher percent of expression and higher H-score (p<0.001 for all) were significantly associated with control skin compared with perilesional skin in follicular and inter-follicular epidermis. Regarding E-cadherin expression, moderate intensity, higher percent of expression and higher H- score (p<0.001 for all) were significantly associated with control skin compared with perilesional skin in follicular and inter-follicular epidermis. No significant association was found between E-cadherin and AQP3 H-scores or percent of expression and clinical data of selected cases. No significant correlation was detected between E-cadherin and AQP3 H-scores or percent of expression and age of cases, disease duration or Vitiligo Disease Activity (VIDA) score. CONCLUSION: The following sequence of events can be suggested for vitiligo pathogenesis, based on findings in perilesional skin: AQP3 is downregulated by a primary unknown factor and this will lead to down regulation of its downstream molecules, mainly phosphatidylinositol 3-kinase, E-cadherin and catenins, which is followed by defective keratinocyte adhesion and decreased release of keratinocyte-derived growth factors. Subsequently a secondary event, physical trauma, oxidative stress or autoantibodies, may lead to exfoliation of keratinocytes and pigmented cells.