Expression of MDM2 mRNA, MDM2, P53 and P16 Proteins in Urothelial Lesions in the View of the WHO 4th 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.

Expression of FGFR3 Protein and Gene Amplification in Urinary Bladder Lesions in Relation to Schistosomiasis.

BACKGROUND: Bladder cancer represents the fifth most common malignancy worldwide and a major cause of cancer-related morbidity and death. Incidence and mortality rates have remained relatively constant over the past four decades. Urothelial bladder cancers have identified multiple risk factors. AIM: We aimed at evaluating the expression of the FGFR3 protein and gene amplification in the urothelial cells of neoplastic and non-neoplastic urothelial lesions of the urinary bladder, and correlation with tumour grade, stage and associated bilharziasis. MATERIAL AND METHODS: One hundred and five different urinary bladder lesions were studied, including 15 cystitis cases (9 bilharzial and 6 non-bilharzial cystitides), 75 urothelial carcinoma cases (18 bilharzial associated and 57 non-bilharzial associated) and 15 squamous cell carcinoma associated with bilharziasis, beside 5 control cases. Data concerning age, sex, tumour grade, stage, and associated bilharziasis were obtained. Each case was studied for FGFR3 expression, and FISH technique was applied on forty malignant cases that show high protein expression. RESULTS: The highest incidence of cystitis was in the fourth decade while of bladder cancer was in the seventh decade. Tumour grade was correlated significantly with tumour stage. FGFR3 correlates significantly with tumour grade, stage and with a bilharzial infestation. FGFR3 gene amplification was reported mainly in low grade and NNMBIC tumours. CONCLUSIONS: FGFR3 overexpression in malignant cases was significantly higher than in chronic cystitis. FGFR3 gene amplification was reported mainly in low grade and NNMBIC tumours. FGFR3 may be further studied as a subject for target therapy of bladder cancer.