FEASIBILITY OF EGFR EVALUATION IN BLADDER WASHINGS OF PATIENTS AFFECTED BY NON MUSCLE-INVASIVE BLADDER CANCER.

Abstract

INTRODUCTION AND OBJECTIVES: Epidermal Growth Factor Receptor (EGFR) overexpression has been recognized as a marker of biological aggressiveness in several malignant neoplasms. EGFR studies on non-muscle invasive bladder cancer (NMIBC) are lacking. Urothelial EGFR status after TUR could provide useful information about the risk of recurrence and progression. The aim of our study was to investigate the feasibility of EGFR evaluation in bladder washings of patients affected by NMIBC correlating its expression to European Association of Urology (EAU) risk classes. METHODS: A prospective double-blinded study included patients undergoing adjuvant intravesical therapy for NMIBC and age-matched healthy controls. Acellular pelletwas obtained and stored at -80C. Isolation of cellular RNA was performed using a miRNeasy Mini Kit (Qiagen) and DNA derived from reverse transcription was used to perform gene expression analysis by a Real Time PCR according to ??Ct method. RESULTS: Fifty-eight patients and 21 controls entered the study. One hundred fifty-three samples were collected. A useful pellet was obtained in 50 patients (86.2%) and 18 controls (85.7%). The mean EGFR expression in 50 NMIBC was 1.94 folds (range: 0.10-8.00). Compared with healthy controls (EGFR¼1), 40 patients (80%) were positive for EGFR. Particularly, in 18 patients (36%) EGFR was overexpressed (EGFR>1.94) with a mean value of 3.61 folds (range: 2.00- 8.00). According to EAU risk groups, EGFR expression was evaluated in low, intermediate and high risk patients respectively. In 20 high risk NMIBC the mean EGFR expression resulted 2.45 folds and 10 of them (50%) presented significant up-regulation with a mean value of 4.10 folds (range: 2.30-8.00). CONCLUSIONS: Our preliminary study demonstrates the feasibility of EGFR determination in bladder washings of patients affected by NMIBC after TUR, during adjuvant treatment and subsequent follow-up. A useful pellet was available in more than 85% of patients, with evidence of up-regulation in 36% of them. Within the high risk category, a significant overexpression of EGFR, mean value of 4.16 folds, was detected. EGFR overexpression might identify a subgroup of high risk tumors inclined to progression despite of intravesical therapy and could represent an additional prognostic factor to select candidates for early radical cystectomy

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