BIOMARKERS OF UROTHELIAL DAMAGE IN PATIENTS TREATED BY ADJUVANT INTRAVESICAL THERAPY

Risultato della ricerca: Other

Abstract

Introduction/Aim: Chemotherapy or BCG given intravesicallyto prevent recurrence after transurethral resection (TUR) ofnon-muscle invasive bladder cancer (NMI-BC) causefrequent, sometime severe, local toxicity. As a consequence,many patients do not complete the planned treatment (1). Amajor challenge for the urologists is to identify an early biomarker of urothelial damage to recognize and prevent localtoxicity improving patient’s compliance. The purpose of ourresearch was to investigate the relation between urothelialinjury by intravesical treatment and the expression ofpotential biomarkers in urine and/or in barbotage solution.The urinary HB-EGF expression in interstitial cystitis hasbeen analyzed by a few studies (2, 3). As a preliminary step,the variations of Fibronectin (FN), Epidermal Growth Factor-Receptor (EGF-R) and Heparin-binding Epidermal GrowthFactor-like Growth Factor (HB-EGF) during intravesicaltherapy and after the administration of a solution with thepotential role of urothelial repairing (hyaluronic acid andchondroitin sulphate) were investigated. Patients andMethods: the toxicity of intravesical therapy with mitomycin,epirubicin or BCG was classified in 3 grades (absent,moderate, severe). Urine and bladder washing solution duringintravesical therapy in 55 patients after NMI-BC TUR and in10 healthy controls for a total of 200 samples were collected.Total cellular RNA was isolated from the cell pellet usingmiRNeasy Mini Kit (Qiagen®). FN and EGF-R geneexpression by Real Time quantitative PCR were analyzed.The expression of HB-EGF was measured in urine samplesby ELISA (Abcam®). Results: In barbotage samples the FNgene expression and the EGF-R levels in our patients wererespectively increased a median of 4.7 fold and decreased of0.9 fold compared to controls. Before intravesical therapy andin absence of local toxicity, gene expression increased 1.9fold for FN and 1.1 fold for EGF-R. In contrast, in patientswith local toxicity due to intravesical therapy, the FN geneexpression levels increased to a median of 5.82 fold, whileEGF-R remained unchanged. The administration ofhyaluronic acid and chondroitin sulphate solution decreasedthe mean FN gene expression from 3 to 0.6 fold, withconcomitant symptomatic relief. HB-EGF protein medianurine levels were 25.7 pg/ml in 13 patients before intravesicaltherapy and 18.9 pg/ml in 5 healthy controls. No significantvariations in relation to the local toxicity. During therapymedian HB-EGF protein levels in urine varied from 21.6pg/ml in absence of toxicity to 25.7 pg/ml in case of severetoxicity to 18.5 pg/ml after hyaluronic acid and chondroitinsulphate solution. Preliminarily, the observed variations ofHB-EGF, increasing no more than 1.2 fold compared tohealthy controls, do not seem possible marker of urothelialdamage. Discussion and Conclusion: EGF-R gene and HBEGFexpressions do not seem to vary significantly in relationto local toxicity due to intravesical therapy. FN gene isoverexpressed in presence of urothelial damage significantlyreduced by intravesical hyaluronic acid and chondroitinsulphate solution administration, according with symptomsrelief.
Lingua originaleEnglish
Pagine2271-2272
Numero di pagine2
Stato di pubblicazionePublished - 2013

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