Expression of MDM2 mRNA, MDM2, P53 and P16 Proteins in Urothelial Lesions in the View of the WHO 4^th Edition Guidelines as a Molecular Insight towards Personalized Medicine

Aim: Here we imposed a multimarker molecular panel composed of P53, MDM2 protein & mRNA & P16 with the identification of sensitive and specific cut offs among the Egyptian urothelial carcinomas bilharzial or not emphasize the pathological and molecular classifications, pathways and prognosis as a privilege for adjuvant therapy.

Methods: Three hundred and ten urothelial lesions were pathologically evaluated and grouped as follows: 50 chronic cystitis as benign, 240 urothelial carcinomas and 20 normal bladder tissue as a control. Immunohistochemistry for MDM Protein, P16 & p53 and In Situ Hybridization for MDM2mRNA were done.

Results: MDM2mRNA overexpression correlated with low grade low stage non invasive tumors, while P53 > 40% & p16 < 10% cut offs correlated with high grade high stage invasive carcinomas & bilharzial tumors (P=0.000).

Conclusion: MDM2mRNA overexpression vs. P53 > 40% & P16 < 10% constitutes a multimarker molecular panel with significant cut offs, proved to distinguish low grade, low stage non invasive urothelial carcinomas (MDM2mRNA overexpression, P53 < 40%, P16 > 10%) from high grade, high stage invasive urothelial carcinomas (with p53 > 40, p16 < 10% & absent MDM2mRNA overexpression). Combined P53 > 40 & p16 < 10%, together with the histopathological features can distinguish in situ urothelial lesions from dysplastic and atypical lesions.