The results of the current study are supported by a study [35] which stated that EGFR is this website associated with SCC of bladder and another study [10] stated that 70% of muscle-invasive bladder cancers express EGFR which is associated with poor prognosis. Accordingly, the current study showed the importance

of EGFR as a candidate for anti-cancer therapy in bladder. It was suggested that there is a need to use CDK inhibitor anti-EGFR as a novel anti-cancer therapy in bladder [11]. In cancer cells, Ki-67 plays an important role as an index for the replication and the prognosis and is well associated to tumor grade, stage and recurrence [36]. In this study, expression of Ki-67 protein was higher in SBT/NSBT than in SC/NSC which was higher than in CTL group. There was no difference in the proliferation rate between SBT and NSBT. Therefore, a limited role of ki-67 might be present in schistosoma-related pathogenesis of bladder cancers. Moreover,

ki-67 was associated with high grade NSBT, invasive SBT, and late stage NSBT. This is in agreement with other studies [37, 38] which showed that Ki-67 positive immunostaining was correlated with tumor grade and muscle invasion. Conclusion Taken together, the molecular background of SBT seems distinct from that of NSBT. SBT was associated with SCC, higher grade and more invasive tumors while NSBT was associated with TCC, lower grade and less invasive tumors. p53, bcl-2, c-myc, Rb, and EGFR were highly expressed in SBT, more than in NSBT, which are therefore might be useful as indicators and discriminatory markers for bladder cancer in general and GS-7977 in vivo SBT in particular. Chronic cystitis acts as an intermediate stage for the overexpression of p53, bcl-2, and EGFR markers that were shown implicated in both SBT and NSBT. p53 is strongly

associated with high grade SCC tumors in both SBT and NSBT but it is poor prognostic factor. Bcl-2 is similar to p53 but it is increased in recurrent cases. P16, Rb, and c-myc were shown as good prognostic markers for SBT and NSBT. C-myc and EGFR appeared central in many aspects of carcinogenesis, Montelukast Sodium tumor grade, tumor invasiveness, and cancer staging. Acknowledgements This study was greatly supported by many medical centers in many countries in the Middle East and in Malaysia where the study was done. We awe the success of this study to the peerless collaboration of the specialist urologists and pathologists in recruiting, examining, diagnosing, and sorting the population of the study correctly and double-blind examining the histopathological tissue sections. References 1. Shirai T: Etiology of bladder cancer. Semin Urol 1993, 3: 113–116. 2. Carroll PR: Urothelial Carcinoma: Cancers of the Bladder Ureter & Renal Pelvis. General Urology 14 Edition (Edited by: Tanagho EA, McAninch JW). Philadelphia: Prentice-Hall International Inc 1995, 353–372. 3.