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Expression of FGFR 3 protein and gene amplification (FISH) in different stages and grades of bladder cancer

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Sources of Funding: none

Introduction

Aim:Evaluation of the expression of FGFR3 protein and gene amplification (FISH) in the urothelial cells of neoplastic and non-neoplastic urothelial lesions of the urinary bladder, and correlation with,hitopathological typpes tumor grade, stage and associated bilharziasis.

Methods

One hundred and five different urinary bladder lesions were studied. Data concerning age, sex, tumor grade, stage, and associated bilharziasis were obtained. Each case was studied using monoclonal antibodies for FGFR3 and examined for detection of immunostaining in urothelial cells_x000D_ and FISH(Flourescent insitu hybridization technique ) technique was applied on 40 malignant cases that shows FGFR3 protein over expression ( more than50% expression og FGFR 3 protien) by immunohitochemistry._x000D_

Results

Histologically, 15 of the cases were diagnosed as chronic cystitis, and the other 90 cases had malignant lesions. Totally, 29.7% of all examined lesions had bilharzial affection._x000D_ Urothelial lesions were more predominant in males (75.6%), Malignant cases comprised TCC (75cases), SCC (15 cases). Sixty percent of TCC cases presented in non muscle invasive stage, while all SCC cases were in muscle invasive stages,62% of TCC cases were of high grades (grade II and grade III) while all cases of SCC are of high grade. ._x000D_ Bilharzial associated malignant lesions were muscle invasive (T2 and T3) in 75.7 % of cases and of high grade (grade II and III) in 84.8 % of cases, while non muscle invasive tumors and low grade tumors presented in 24.3% and 15.2% of non bilharzial malignant tumors respectively._x000D_ Bilharzial association in TCC cases was in 24% of cases, While all cases of SCC were associated with bilharziasis._x000D_ All five control cases were negative for FGFR3 immunostaining. Sixty six percent of chronic cystitis cases were positive for FGFR3immunostaining, while in malignant cases 67.8% were FGFR3positive with significant increase in staining extent versus chronic cystitis cases. _x000D_ Non bilharzial chronic cystitis cases were 66.6% positive for FGFR3 immunostaining and 66.6% of bilharzial cystitis cases expressed FGFR3 . This incidence of FGFR3 expression raised significantly in malignant cases to involve 54.5% of them. _x000D_ Seventy two percent of TCC cases were positive for FGFR3 while 7 cases of SCC were positive for FGFR3 ._x000D_ Staining intensity of FGFR3 in bilharzial associated malignant lesions were mainly of mild and moderate intensity(36% and 15% ), while in non bilharzial malignant lesions it was mainly of mild intensity (66.6% )._x000D_ FISH technique was applied on forty cases in malignant group with overexpression of FGFR3 protein. There are 36 malignant cases out of 40 cases show amplified FGFR3 gene, There were 88.2% of TCC cases show FGFR3 gene amplification most were of low grade (70%) and show significant difference at p value < 0.01 compared to high grade, and in NMIBC group (80%) ( p value <0.01)._x000D_

Conclusions

Estimation of FGFR3 expression can serve as a prognostic indicator in follow up of cancer bladder patients , especially in bilharzial associated malignant cases._x000D_ Expression of FGFR3 could be utilized for molecular targeted therapy in urinary bladder cancer._x000D_ To our knowledge,this is the first study to assess FGFR 3 protein gene amplification (FISH)in SCC of the bladder._x000D_ _x000D_

Funding

none

Authors
Hosni Salem
Amira kamel
Tarek Aboushousha
Olfat Hammam
Ali El-Hindawi
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