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Background: Urothelial carcinoma of the urinary bladder is the second most common malignancy of the genitourinary system, after prostate cancer. The flat lesions are classified into flat lesions without cytological atypia (Flat hyperplasia) and flat lesions with cytological atypia; reactive atypia, atypia of unknown significance, urothelial dysplasia and urothelial carcinoma in situ). The immunohistochemical markers such as cytokeratin 20,CD 44 and Ki 67 may be useful in differentiating CIS from reactive changes in difficult biopsy cases. Aim: This study was conducted to determine the role of cytokeratin 20, CD 44 and Ki 67 in the diagnosis of dysplasia and other flat lesions of the urinary bladder. Methods: Sixty representative cases for flat urothelial lesions of urinary bladder were examined immunohistochemically using antibodies against CD44, cytokeratin 20 and Ki-67. Results: CD 44 were positive in 100%of cases of reactive urothelial atypia, but flat Hyperplasia and CIS cases were negative. However CD 44 were positive in 42.9% of atypia of unknown significance and 14.3% of Dysplasia. CK 20 were positive in (95.5%) of Dysplasia. Non of Flat Hyperplasia were positive for CK 20. However CK 20 was positive in 88.2% of CIS, 57.1 % of atypia of unknown significance and 7.1% of reactive urothelial atypia. ki 67 index were high in 82.4% of cases of CIS, non of flat hyperplasia expressed high ki 67 index. However ki 67 index were high in 57.1% of atypia of unknown significance, 52.4% of dysplasia and 14.3% of reactive urothelial atypia. Conclusion. CD 44 is the most constant marker in the reactive urothelium. CK20 is the most commonly detected marker in the dysplastic urothelium. Nevertheless, the most accurate is application of an immunohistochemical panel composed of the three antibodies (standard CD 44, CK20 and Ki-67) together with correlation with morphology. This is very useful for confirming the presence of dysplastic changes in the urothelium and differentiating reactive urothelium from dysplastic urothelium (dysplasia/CIS). Keywords: Flat epithelial lesions, CD44, cytokeratin ck20, ki67, immunohistochemistry.

SIGNIFICANCE OF FLAT EPITHELIAL LESIONS OF THE URINARY BLADDER IN EARLY DETECTION OF BLADDER CANCER: HISTOPATHOLOGICAL AND IMMUNOHISTOCHEMICAL STUDY