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

Abstract

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.

Immunohistochemical Expression of Fibroblast Growth Factor Receptor 3 and Cyclooxygenase-2 in Urinary Bladder Carcinomas with Correlation of Schistosomiasis in Egyptian Patients

“…As for immunostaining for FGFR-3 expression, the current study showed that only 24 cases showed negative staining and the remaining 66 cases (73.3% of total cases) showed positive cytoplasmic and/or membranous. Hammam et al [11] also found that 72% of malignant cases in their study were also positive for FGFR3 immunostaining, which is compatible with another study [10] that stated that expression of FGFR3 was found in approximately 70% of both low and high-grade tumors, as well as equally distributed between invasive and non-invasive urothelial carcinoma. Evaluation of the results of immunostaining for COX-2 showed that only 15 cases were negative with the remaining 75 cases (83.3% of total cases) showed positive cytoplasmic and/or membranous reactivity.…”

“…On the other hand, this study displayed no linear correlation between COX-2 expression and tumor size. Thus, these interesting results similarly supported by Hammam et al [11], who argued that COX-2 may have more of a tumorigenic role rather than a prognostic impact.…”

“…In relation to FGFR3, Hammam et al [11] showed that 54.5% of their study cases showed FGFR3 immunostaining and demonstrated a positive correlation of bilharzial bladder cancers and FGFR-3 (p ≤ 0.001). Further Chi-square analytical studies were performed to show if a relation between COX2 and FGFR3 exists between the schistosomal-associated cases, in which positive correlation was established between the bilharzial-associated low-grade COX2 and FGFR3 cases (p = 0.025, p = 0.028), respectively.…”

Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling

“…FGFR3 and FGFR4 amplifications are less common and less well studied than FGFR1 and FGFR2 amplifications. FGFR3 amplification is the most common FGFR amplification event in urothelial/bladder cancer [ 189 , 206 , 207 , 208 ].…”

Is Schistosomiasis a Risk Factor for Bladder Cancer? Evidence-Based Facts

“…However, in North Africa, especially Egypt, major strides have been made over the years to establish the molecular basis of schistosomiasis and bladder cancer. A case-control study by Hammam et al [23] in Egypt assessing the expression of the fibroblast growth factor receptor (FGFR3) protein, gene amplification in bladder cancer, and associated schistosomiasis revealed that FGFR3 was considerably associated with bladder cancer tumor-grade and stage. Another data from Egypt by Elmansy et al [24] assessing association of Fas and FasL in human bladder cancer with schistosomiasis found that the association of schistosomiasis with bladder cancer raised the incidence of Fas positive immunoreactivity to 100%.…”