FIBRONECTIN (FN) AND UROTHELIALDAMAGE SECONDARY TO ADJUVANTINTRAVESICAL THERAPY

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Abstract

Introduction and Objectives: Intravesical chemotherapy hasbeen proven effective in preventing recurrence of low-risknon-muscle invasive bladder cancer (NMIBC). BCG is recognised as the best conservative treatment for intermediateand high risk NMIBC. Maintenance for at least one year isrequired to ameliorate the efficacy of adjuvant therapy.Discomfort and toxicity often cause interruption of adjuvanttherapy, BCG particularly. Almost 50% of the patientsundergoing BCG does not complete one year. A biomarker ofurothelium damage would be helpful for timely detection oftoxicity in order to ameliorate patient’s tolerance andcompliance. The aim of the present study was to evaluate thegene expression of Fibronectin (FN) in bladder washing inrelation with local toxicity due to adjuvant intravesical therapy.Patients and Methods: Out of 26 asymptomatic patientsundergoing intravesical prophylaxis with mitomycin (40mg/40 ml), epirubicin (80 mg/50 ml) or BCG Connaught (81mg/50 ml) and 10 volunteers as control group, 62 samples ofbladder washing were collected before, during and aftertherapy. The samples were analyzed by isolation of cellularRNA using a miRNeasy Mini Kit (Qiagen®). FN geneexpression was analyzed by RT-PCR. The ΔΔCt method afternormalization with endogenous reference 18s rRNA wasadopted. An average Ct value for each RNA was obtained fortriplicate reactions. Local toxicity was classified into 3 grades:0-1. mild (no medical therapy); 2. moderate (medical therapy);3. severe (instillation postponed for 1-2 weeks or intravesicalsolution of hyaluronic acid and chondroitin sulphateadministered). Results: FN gene expression, compared tocontrols, was increased 1.1 fold after TUR and beforeintravesical therapy. During therapy it remained unchanged(1.0 fold). However it was increased 1.1 fold in absence oflocal toxicity, but to a median value of 3.6 fold in presence ofsevere toxicity. Particularly, the mean values, compared tocontrols, were 2.4 (range: 0.3-6.1), 1.1 (range: 0.1-2.3), 9.3(range: 0.2-45.2), before therapy, in absence and in presenceof local toxicity, respectively. Of interest, patients receivingintravesical hyaluronic acid and chondroitin sulphate solutionshowed a median FN gene expression of 0.2 fold (range 0.1-0.7), decreasing from 3 to 0.6 and from 4 to 0.2 fold in twopatients contemporary with symptomatic relief. Discussion:Few studies have correlated the gene expression of FN tobladder urothelial damage, in interstitial cystitis (1). FN playsan important role on BCG activity (2). A marker of topicaltoxicity would be helpful to improve the tolerance and toreduce the drop-out rates of intravesical therapy. Themeasurement in bladder washing is a simple and directevaluation of urothelial FN gene activity. This method avoidsall the bias due to the evaluation of FN protein expression inurine. The overexpression of FN gene indicates the presenceof urothelial damage and activation of repairing processes.Normal and downexpression indicate the absence or healingof urothelial damage. Preliminarily, our study shows asignificant correlation between FN gene expression on bladderwashing and local toxicity. Furthermore, FN seems to bereduced by the intravesical administration of intravesical hyaluronic acid and chondroitin sulphate solution. Conclusion:FN gene expression in bladder washing emerges as a simpleand promising marker of urothelial damage. Further and largerstudies should be justified.Acknowledgements: We wish to thank IBSA for unrestricted grantand the GSTU Foundation for administrative support.1 Blalock EM et al: Gene expression
Lingua originaleEnglish
Pagine2613-2614
Numero di pagine2
Stato di pubblicazionePublished - 2014

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