EGFR CELL EXPRESSION IN BLADDER WASHINGS AS A RISK MARKER TOOL IN NON MUSCLE-INVASIVE BLADDER CANCER. PRELIMINARY EXPERIENCE

INTRODUCTION AND OBJECTIVES: Up to day, EGFR expression has been determined mainly in tissue specimens of muscleinvasive bladder cancer and its overexpression has been associated with worse prognosis and shorter survival. Urothelial EGFR status after NMIBC transurethral resection (TUR) could indicate the risk of recurrence and progression. We investigated the feasibility of EGFR measurement in bladder washings of patients undergoing intravesical adjuvant therapy for NMIBC and its usefulness in identifying risk subgroups. METHODS: Our prospective study included patients after TUR of NMIBC and healthy controls. A cellular pellet was obtained from bladder washing, and RNA extraction performed by miRNeasy Mini Kit (Qiagen). Good quality of RNA was checked. The cDNA obtained from RNA was used to perform a gene expression analysis by a Real Time PCR, according to the method of the comparative quantification (DDCt) with an endogenous control (Cyclophilin). Every reaction was set in triplicate as a guarantee of quality. Patients were grouped for EAU risk class and maintained in follow-up. The EGFR expressions were statistically analyzed according to EAU risk groups and to patients0 outcome. EGFR gene expression values were expressed in FOLDs of change compared to healthy controls (EGFR¼1). RESULTS: Fifty-eight patients and 21 healthy age-matched controls were entered. An adequate cellular pellet was obtained in 50 patients (86.2%) showing a median EGFR expression of 2.0 folds (IQR 0.6-4.3, p¼0.0004). After TUR and adjuvant intravesical therapy, 22 (55%) out of 40 high-risk patients, showed EGFR decrease to 1.3 folds (IQR 0.9-1.5), while 18 (45%) showed elevated EGFR, median 4.7 (IQR 4.1-11.6). At 25 months median follow-up (IQR 19.0-34.8), 20 (40%) patients recurred and 6 (12%) progressed. Among patients with or without EGFR gene increase, 9 (22.5%) and 5 (12.5%) recurred and 5 (12.5%) and 1 (2.5%) progressed, respectively. CONCLUSIONS: In our experience EGFR expression measurement was feasible in more than 85% of patients and resulted related to EAU risk classes for recurrence and progression, showing different behavior during intravesical therapy. It was possible to identify a subgroup of high risk patients overexpressing EGFR in spite of intravesical adjuvant therapy. EGFR evaluation in bladder washing could represent a repeatable and useful tool to identify a subgroup of patients at risk for progression unresponsive to intravesical adjuvant therapy and candidate to early radical cystectom