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. 2017 Aug 5;5(5):578-586.
doi: 10.3889/oamjms.2017.100. eCollection 2017 Aug 15.

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

Olfat Hammam  1 , Mona Magdy  1 , Mohamed Badawy  2 , Khalid Al Osili  2 , Amr El Kholy  2 , Tarek El LeitHy  2
Affiliations

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

Olfat Hammam et al. Open Access Maced J Med Sci. .

Abstract

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.

Keywords: MDM2mRNA; P16; P53; bilharzia; grade; urothelial.

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Figures

Figure 1
Figure 1
Immunohistochemistry expression of the MDM2 protein, P53 & P16. (IHC, DAB, ×200). (A) Control case showing negative expression of MDM2 antibody; (B) High grade (G2) invasive papillary urothelial carcinoma, showing P53> 40% nuclear expression, (in focus); (C) High grade (G3) invasive urothelial carcinoma showing P53 > 40% nuclear expression in the squamous cells (in focus); (D) High grade (G2) SQCC showing moderate number of nuclei positive for MDM2 antibody in the squamous cells (in focus); (E) Control case expressing p16 antibody (in focus); (F) Low grade papillary urothelial carcinoma, showing large number (> 10%) of nuclei positive for p16 antibody, (in focus); (G) High grade (G3) invasive urothelial carcinoma showing few (< 10%) of nuclei positive for p16 antibody in the squamous cells; (H) High grade (G2) showing positivity (> 20%) for MDM2 antibody
Figure 2
Figure 2
ISH staining for MDM2mRNA. (A–D) ISH; x625. (A) Normal expression in a control case, showing negative expression of MDM2 mRNA in the urothelium. (B) Low grade papillary, noninvasive (G1) UC showing (+++) green signal for MDM2mRNA (overexpression) in a urothelial cells (red arrow). (C) High grade SQCC G2-3 showing a moderate (++) green signal for MDM2 mRNA in urothelial cells (red arrow). (D) High grade invasive UC associated with bilharziasis showing mild (+) green signal for MDM2 mRNA in a urothelial cells (red arrow), bilharzial ova (yellow arrow)
Figure 3
Figure 3
Percentage of expression of MDM2 (protein & mRNA), P53 & P16 scores. (A) Among the studied groups; (B) Regarding tumour type; (C) Regarding bilharzia association in tumours
Figure 4
Figure 4
Percentage of expression of MDM2 (protein & mRNA), P53 & P16 scores. (A) Regarding tumour grade; (B) Regarding tumour stage; (C) Regarding invasion
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