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

Chromosomal aberrations in benign and malignant Bilharzia-associated bladder lesions analyzed by comparative genomic hybridization

BACKGROUND: Bilharzia-associated bladder cancer (BAC) is a major health problem in countries where urinary schistosomiasis is endemic. Characterization of the genetic alterations in this cancer might enhance our understanding of the pathogenic mechanisms of the disease but, in contrast to nonbilharzia bladder cancer, BAC has rarely been the object of such scrutiny. In the present study, we aimed to characterize chromosomal imbalances in benign and malignant post-bilharzial lesions, and to determine whether their unique etiology yields a distinct cytogenetic profile as compared to chemically induced bladder tumors. METHODS: DNAs from 20 archival paraffin-embedded post-bilharzial bladder lesions (6 benign and 14 malignant) obtained from Sudanese patients (12 males and 8 females) with a history of urinary bilharziasis were investigated for chromosomal imbalances using comparative genomic hybridization (CGH). Subsequent FISH analysis with pericentromeric probes was performed on paraffin sections of the same cases to confirm the CGH results. RESULTS: Seven of the 20 lesions (6 carcinomas and one granuloma) showed chromosomal imbalances varying from 1 to 6 changes. The most common chromosomal imbalances detected were losses of 1p21-31, 8p21-pter, and 9p and gain of 19p material, seen in three cases each, including the benign lesion. CONCLUSION: Most of the detected imbalances have been repeatedly reported in non-bilharzial bladder carcinomas, suggesting that the cytogenetic profiles of chemical- and bilharzia-induced carcinomas are largely similar. However, loss of 9p seems to be more ubiquitous in BAC than in bladder cancer in industrialized countries

Past (1950–2017) and future (−2100) temperature and precipitation trends in Egypt

International audienceEgypt, located in the Middle East and North Africa region, is considered to be a potential hot-spot of climate change where the warming and increase of the frequency of extreme temperatures could occur faster than at global scale. Precipitation is also expected to decrease in the region. In this work, our aim is to quantify the past and future temperature and precipitation trends at 8 locations selected for being representative of the variety of Egyptian climates. For the past period (1950–2017), we show that the decadal temperature trends derived from the analysis of the assimilated ERA-Interim (ERA-Int) and downscaled CORDEX (Historical and Evaluation) data are consistent. Relative to 1960, the daily maximal and minimal temperatures have increased by 1.3 ± 0.1 and 1.3 ± 0.3 °C, respectively, at the 8 selected locations. However, at the shorter yearly time scale, sub-regional differences of climate variability can be evidenced: this variability is less at the coastal and Nile Delta sites than at the drier inland locations. For the future, we use an ensemble of 6 CORDEX Africa models. Under the RCP45 scenario, the temperatures are predicted to increase at a rate ranging from 0.28 ± 0.04 °C/decade (Alexandria) to 0.38 ± 0.09 °C/decade (Hurghada and Aswan) between 2010 and 2040, and to abate afterwards (0.12 ± 0.08 °C/decade). Under the RCP85 scenario, the rates of temperature increase before 2040 are similar to those under RCP45 (from 0.24 ± 0.14 to 0.40 ± 0.12 °C/decade) but considerably larger afterwards (from 0.48 ± 0.18 °C to 0.72 ± 0.11 °C/decade between 2050 and 2100). As compared to the 2006–2015 reference period, the extreme temperatures analysis performed with the CLIMDEX software shows that the hot days and nights will become more frequent at all sites, but that the increase will occur at larger rates at the Red Sea (Hurghada) and upper Egypt (Aswan) sites than at the other ones. These inter-site differences are more pronounced with RCP45 than with RCP85. Considering the latter scenario, in the last decade of this century about 80% of the days in a year would be hotter than the 90th percentile of the 2006–2015 reference period. Regarding the annual precipitation, the analysis of ERA-Interim data of the 1980–2017 period does not reveal any significant trend, but in both RCP45 and RCP85 a significant decrease (from −0.48 to −0.9 mm/y, and from −0.95 to −1.40 mm/y, respectively) is predicted to occur from 2010 to 2100 in the north of Egypt where rain is currently the most abundant