الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Bladder cancer (BC) is the most common malignancy involving the urinary system and the ninth most common malignancy worldwide. It ranks ninth in worldwide cancer incidence, fourth commonest cancer in men and 12th in women. In Egypt, bladder cancer is the third common malignancy accounting for 14.3 % according to National cancer registry, 2016.
Investigating the role of ROC-I in the cell cycle regulation via P21 together with the role of hypoxic marker CAIX in bladder cancer and their correlation with clinicopathological prognostic parameters, is the aim of the present study.
Using the standard IHC technique, we assessed ROC-I, CAIX and P21 expressions in 80 bladder carcinoma cases and 15 urothelial specimens (control group). The cases were retrieved from the archives of Pathology Department, Faculty of Medicine, Menoufia University spanning the period between January 2014 and December 2016.
In the present study, the age of the patients ranged from 45 to 96 years old with a mean of 62. Seventy-two cases (90%) of the studied primary bladder carcinoma were males and eight cases (10%) were females with M:
F ratio of 8:1. The size of the tumor ranged from 1-10 cm with a mean of
4.64.
Regarding the histologic type of bladder carcinoma 90% were diagnosed as UC (infiltrating UC and UC with divergent differentiation) and according to the grade of infiltrating urothelial carcinoma 80.6% were high grade. Regarding TNM staging; 62.5% were advanced (T2, 3, 4) and
37.5% were early stage (T l) and 50% had LN invasion (NI , 2).
About 20—30% of all newly diagnosed bladder cancers exhibit a type of muscle layer invasion known as muscle-invasive bladder cancers (MIBCS). In addition, 10—30% of non-muscle-invasive bladder cancers (NMIBCS) will eventually progress to muscle invasive. Furthermore, even with chemotherapy after surgery, progression and recurrence occur in the majority of MI-BCs patients, leading to poor prognosis. So far, effective predictive tools are absent for bladder cancer after surgical procedures. So, identification of BC specific disease-related biomarkers that can predict the clinical outcome and be anticancer targets is of great importance and urgently needed.
ROC-I is a key Cullin Ring Ligase (CRL); forming its catalytic core and has an important role in the ubiquitination of many proteins. ROC-I overexpression has been linked to tumor development and progression. In the present study, ROC-I showed expression in 90% of the bladder cancer cases and 93% normal urothelial tissues.
In the present study, positive expression of ROC-I in the malignant group was significantly associated with poor prognostic factors in BC as high grade UC (P=0.04) and near significant with advanced pathological stage T4 (P=0.07). Moreover stepwise increase of ROC*I from early to advanced BC implies its potential role in BC progression.