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

Nuclear Localization of COX-2 in relation to the Expression of Stemness Markers in Urinary Bladder Cancer

Inflammation may activate stem cells via prostaglandin E2 (PGE2) production mediated by cyclooxygenase-2 (COX-2) expression. We performed an immunohistochemical analysis of the expression of stemness markers (Oct3/4 and CD44v6) and COX-2 in urinary bladder tissues obtained from cystitis and cancer patients with and without Schistosoma haematobium infections. Immunoreactivity to Oct3/4 was significantly higher in S. haematobium-associated cystitis and cancer tissues than in normal tissues. CD44v6 expression was significantly higher in bladder cancer without S. haematobium than in normal tissues. COX-2 was located in the cytoplasmic membrane, cytoplasm, and nucleus of the cancer cells. Interestingly, the nuclear localization of COX-2, which was reported to function as a transcription factor, was significantly associated with the upregulation of Oct3/4 and CD44v6 in bladder cancer tissues with and without S. haematobium infection, respectively. COX-2 activation may be involved in inflammation-mediated stem cell proliferation/differentiation in urinary bladder carcinogenesis

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

Sequential chemoimmunotherapy using mitomycin followed by bacillus Calmette-Guerin (MCC + BCG) versus single-agent immunotherapy (BCG) for recurrent superficial bladder tumors

INTRODUCTION: The purpose of the present study was to compare the outcomes of patients receiving sequential chemoimmunotherapy using mitomycin (MMC) and bacillus Calmette-Guerin (BCG) with the outcomes of patients receiving BCG alone for the treatment of recurrent superficial bladder tumors. METHODS: A total of 56 patients with recurrent Ta or T1 bladder tumors were enrolled in this prospective randomized study. Group 1 (n = 29 patients) received MMC instillation immediately after resection followed by weekly instillation for 4 weeks. Patients then received BCG monthly for 1 year. Group 2 (n = 27) received only BCG, instilled weekly for 6 weeks and then monthly for 1 year. RESULTS: There was a significant treatment effect for both groups, as indicated by a reduction in mean recurrence rate and recurrence index (P = .001). However, the difference in recurrence rate and recurrence index distributions after treatment was significant in favor of group 1. The mean follow-up period was 24 months (range, 3-30 months). Recurrent tumors were found in 9 patients (31%) in group 1 and 16 patients (70%) in group 2 at the end of the follow-up period. Kaplan-Meier estimates were significantly different throughout the follow-up period. MMC followed by monthly BCG was significantly superior to BCG in the time to initial recurrence (log rank P \u3c.0024). CONCLUSIONS: Patients receiving BCG single-agent immunotherapy and patients receiving sequential chemoimmunotherapy using MMC instillations followed by monthly BCG instillation both had significant treatment effects. However, the difference in recurrence rate and recurrence index distributions after treatment was significant in favor of the group receiving the sequential therapy. © 2010 UroToday International Journal

Incidence and predictive factors of radiation‐induced hypothyroidism in breast cancer patients who receive supraclavicular lymph nodes irradiation: A prospective study

Abstract Purpose This paper aimed to assess the incidence of radiotherapy‐induced hypothyroidism (RIHT) in breast cancer patients and correlate it with different factors. Methods Patients with nonmetastatic breast cancer who received supraclavicular lymph node irradiation as a part of adjuvant radiotherapy from October 2019 to July 2020 were recruited and followed up for 18 months. All patients underwent three‐dimensional conformal radiotherapy and underwent computed tomography simulation. The levels of serum thyroid‐stimulating hormone (TSH), free triiodothyronine and free thyroxine levels were assessed at baseline (before starting radiotherapy) and 9,12, and 18 months after radiotherapy using immunochemilluminescence. Univariate and multivariate analyses were performed to identify significant factors associated with developing hypothyroidism. Results Twenty patients out of 96 (20.8%) developed hypothyroidism. Baseline TSH (cutoff value >1.42 μIU/ml) was significantly correlated with hypothyroidism. Conclusion Routine thyroid function tests assessment is recommended for all breast cancer patients at baseline and after radiotherapy