Source of Funding: Translational Science DevelopmentalCancer Research Award, Stanford University.

1073RELEVANCE OF MTOR PATHWAY IN PROGNOSIS OFPATIENTS WITH UROTHELIAL CARCINOMA OF THE BLADDER

Mona Fahmy, Jose Mansure, Fadi Brimo, Faysal Yafi*,Aabdulaziz Althunayan, Robert Segal, Montreal, Canada; George Netto,Alan Meeker, Jessica Hicks, Baltimore, MD; Wassim Kassouf,Montreal, Canada

INTRODUCTION AND OBJECTIVES: To investigate the role ofmTOR signalling pathway on stage and outcome of patients with highgrade and/or invasive bladder cancer.

METHODS: Tissue microarrays were built from archival of highgrade and mostly superficial bladder tumour specimens (n�143 withcomplete clinical data collected). Immunohistochemical staining wasperformed for Phosphatase and tensin homolog (Pten), phosphorylated(phos) Akt, phos-mTOR, phos-S6, phos-4EBP1 and p27. The markerswere evaluated for pattern, percentage and intensity of staining (H-score), and results correlated with clinicopathological characteristicsand outcome.

RESULTS: The median age at diagnosis of the patient cohortwas 71 years (range: 38-96 years). The TNM stage group was distrib-uted as pTa (44%), pT1 (49%) and pT2 (6%). After a median follow-upof 34 months, the disease recurrence, disease progression and overalldeath rates were 44%, 13%, and 11% respectively. The expression ofp27 was significantly lower among pT2 compared to pTa and pT1patients (p � 0.03). The H-score of phos-mTOR was significantlycorrelated with p27 (p � 0.003), pS6 (p � 0.004) and 4EBP1 (p �0.001). In multivariate analysis, which included age, number of tumors,tumor size and stage, phos-S6 was an independent predictor of shorterrecurrence-free (Hazard Ratio [HR]: 2.75, 95% Confidence Interval[CI]: 1.16-6.51). The expression of p27 was inversely correlated withrecurrence-free survival (HR:0.37, 95% CI:0.18-0.88). None of themarkers showed correlation with progression free survival and overallsurvival.

CONCLUSIONS: Our results demonstrate that activation ofmTOR pathway, as assessed by phosS6 might be used to provideprognostic information particularly as predictor of recurrence amongpatients with high-risk non-muscle invasive bladder cancer.

Source of Funding: CIHR

1074FOXP3 EXPRESSION CORRELATES WITH SURVIVAL INUROTHELIAL CARCINOMA OF THE BLADDER

Zhang Hanwei, Xiaoyan Wang, David Seligson, Allan Pantuck,Arnold Chin*, Los Angeles, CA

INTRODUCTION AND OBJECTIVES: The transcription factorForkhead box p3 (Foxp3), originally described during the developmentof CD4�CD25� T regulatory cells, has recently been implicated indivergent roles in human prostate, breast, pancreatic cancer, andmelanoma. Here, we investigate the inducibility of Foxp3 in bladdercancer models and assess the prognostic role of Foxp3 in patients withbladder cancer.

METHODS: Foxp3 expression in the human bladder cancer cellline SW780 was examined in in vitro cultures by flow cytometry and inin vivo subcutaneous implanted tumor models in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice by immunohistochemistry. Proliferationand invasion of SW780 cells in the absence of Foxp3 was performed bytransfection of siRNA in vitro. Correlation of Foxp3 expression tourothelial carcinoma grade, stage, recurrence-free survival, and overallsurvival was examined in a human tumor microarray from a cohort of280 patients by Cox proportional hazards regression and Kaplan-Meieranalysis.

RESULTS: Foxp3 expression correlates to higher cellular pro-liferation in vitro and in vivo. Knockdown of Foxp3 in SW780 cellsresulted in decreased proliferation as well as invasion in vitro. Foxp3expression increases with higher T stage, but not grade, as expressionin adjacent normal bladder, Tis, Ta-1, T2-4, and lymph node metastasiswas 1.2%, 3.8%, 15.2%, 26.5%, and 23.4% respectively, suggestinghigher expression in muscle invasive and lymph node metastatic dis-ease, but not carcinoma in situ. Using a cutoff of 10%, Foxp3 expres-sion negatively correlates with survival following radical cystectomywith a median survival of 9.3 vs 2.8 years and a 10-year survivalprobability of 47% vs 27%.

CONCLUSIONS: This work implicates Foxp3 as novel tran-scription factor driving proliferation and tumor invasion in urothelialcarcinoma. Expression of Foxp3 correlates with T stage and is a novelpredictor of overall survival following radical cystectomy. Future studieswill need to understand the mechanistic regulation of Foxp3 expres-sion, as well examine Foxp3-mediated gene expression in urothelialcarcinoma. Foxp3 expression may improve selection of patients totherapy.

Source of Funding: American Association of Cancer Research

1075HEAT SHOCK PROTEIN 70 (HSP70) AND FGFR3 IN NONMUSCLE INVASIVE BLADDER CANCER TREATED WITH BCG:GENE EXPRESSION AND PROTEIN EXPRESSION ANALYSISUSING 2 DIFFERENT VALIDATION COHORTS

Bas WG van Rhijn*, Oleksandr Stakhovskyi, David Margel,Theodorus van der Kwast, Peter J Bostrom, John Thoms,Robert G Bristow, Michael Milosevic, Neil E Fleshner, Michael AS Jewett,Bharati Bapat, Toronto, Canada; Wun-Jae Kim, Chungbuk, Korea,Republic of; Alexandre R Zlotta, Toronto, Canada

INTRODUCTION AND OBJECTIVES: We previously demon-strated that FGFR3 mutation and protein overexpression selectivelyidentifies pT1 bladder cancer (BC) patients with favorable diseasecharacteristics. However, FGFR3 protein over-expression in the ab-sence of a FGFR3 mutation was not associated with favourable dis-ease characteristics. Heat shock proteins (HSPs) have been implicatedin BC prognosis. Here, we evaluated FGFR3 and HSP70 expression atthe gene and protein levels and their relationship to pathological andclinical parameters using 2 different cohorts of non muscle invasive BCtreated with BCG.

METHODS: 66 primary T1 and 12 Ta BC tumors (confirmed bypathological review) treated at the University Health Network, Torontowere included in the study. Microarrays were built and HSP70 protein

e436 THE JOURNAL OF UROLOGY� Vol. 187, No. 4S, Supplement, Monday, May 21, 2012

expression was determined by standard immunohistochemistry (HSP70Antibody, StressMarq Biosciences Inc, BC, Canada). Slides were co-reviewed with an experienced uro-pathologist with scored dependent onexpression and intensity of the marker. Mutation status was examined bymultiplex PCR-SNaPshot analysis. In the Seoul, South Korea cohort, 68patients without tumor, 23 primary Ta, and 80 pT1 BC treated with BCGwere analyzed using microarray gene expression profiling and RT-PCRanalysis (Illumina HumanWG-6 BeadChip, Illumina, Inc) and Rotor Gene3000 PCR system using SYBR Premix EX Taq (TaKaRa Bio, Inc).Kaplan-Meier method and multivariate Cox-regression analysis were usedfor data analysis.

RESULTS: In Toronto, FGFR3 was mutated in 80% of Tatumors, 42% of T1 LG and 21% of T1 HG (p�0.05). Over 90% of Ta/T1mutant FGFR3 displayed protein overexpression, but also 50% of wildtype overexpressed the protein. In Seoul, FGFR3 gene expression wassignificantly increased in normal vs Ta tumors (p�0.039), normal vs T1LG (p�0.0001) but not significant comparing normal vs T1 HG(p�0.57). Regarding HSP70, Kaplan-Meier survival analysis demon-strated that the lack of HSP70 expression in Toronto and gene expres-sion levels in Seoul were significant predictors for disease recurrence(p�0.05 and 0.015, respectively). HSP70 was shown to correlate withFGFR3 expression and mutation (p�0.05). FGFR3 and HSP70 had noinfluence on tumor progression in both cohorts.

CONCLUSIONS: In 2 different patient cohorts, analyzing geneand protein expression status, both HSP70 and FGFR3 were demon-strated to play an important prognostic role in T1 BC identifying a groupat lower risk of recurrence.

Source of Funding: None

Infections/Inflammation of the Genitourinary Tract:Prostate & Genitalia

Moderated Poster

Monday, May 21, 2012 1:00 PM-3:00 PM

1076COMPARISON OF PROSTATIC ABSCESS TREATMENT: ISTRANSURETHRAL RESECTION OF PROSTATIC ABSCESSMORE EFFECTIVE THAN NEEDLE ASPIRATION?

Seung Hwan Lee*, Dae Hun Lee, Dong Hoon Lee, Kyung Kgi Park,Mun Su Chung, Byung Ha Chung, Seoul, Korea, Republic of

INTRODUCTION AND OBJECTIVES: We aimed to know theeffective treatment of prostatic abscess among conservative treat-ments, transurethral resection of prostatic abscess, and transrectalultrasound (TRUS)-guided needle aspiration in 52 cases over a 10 yearperiod.

METHODS: Between January 2000 and September 2010, therecords of 52 patients diagnosed with prostatic abscess were retro-spectively reviewed. Multivariate regression analysis was done to de-termine independent risk factors for the length of hospitalization inpatients with prostatic abscess.

RESULTS: The mean age at diagnosis was 56.9 years old, themean volume of the prostate was 47cc, the mean PSA was 16.3ng/ml,and the mean prostatic abscess size was 3.8cm. The mean hospitalstay was 17.5 days .19 patients had hypertension (36.5%), 22 haddiabetes mellitus (42.3%), and 7 (13.5%) had paraplegia due to spinalcord injury. The most common symptoms were fever (90.4%), perinealdiscomfort (82.7%), dysuria (76.9%), and urinary retention (55.8%).Conservative treatment in 11 cases, transurethral resection of prostaticabscess in 23 cases, and TRUS-guided needle aspiration in 18 caseswas done respectively. Prostatic abscesses were recurred in 4 cases(22.2%) after needle aspiration within 1 month. And 2 patients per-formed conservative treatment died due to sepsis. On multivariate

regression analysis, age, history of diabetes mellitus, and treatmentmethod of prostatic abscess are the independent factors which affectthe average hospitalization period.

CONCLUSIONS: Considering the mortality of prostatic ab-scess, transurethral resection of the prostatic abscess is the mosteffective method to reduce the time period of hospitalization andrecurrence.

Significant predictors of hospital stay in patients with prostatic abscess

VariablesStandardized regression

coefficient (R) P valueAge 0.492 0.035

DM (yes) 2.124 0.042

Hypertension (yes) 1.016 0.122

Treatment methods

TURP�0 2.293 0.033

Conservative treatment �1

TURP�0, Needle aspiration�1 2.428 0.026

Conservative treatment �0 1.168 0.137

Needle aspiration�1

Urine analysis 0.215 0.079

Leukocytosis 0.172 0.099

Abscess size 0.113 0.189

Prostate volume 0.095 0.245

Source of Funding: None

1077EMPIRIC ANTIBIOTICS FOR AN ELEVATED PSA: ARANDOMIZED, PROSPECTIVE MULTI-INSTITUTIONAL TRIAL

Scott Eggener, Michael Large*, Glenn Gerber, Chicago, IL;Joseph Pettus, John Smith, Winston-Salem, NC; Ofer Yossepowitch,Tel Aviv, Israel; Norm Smith, Shilajit Kundu, Chicago, IL; Jay Raman,Hershey, PA

INTRODUCTION AND OBJECTIVES: The impact of an empiriccourse of antibiotics for a newly elevated PSA in an asymptomatic maleis poorly understood.

METHODS: Men of any age with a PSA � 2.5 ng/ml and normaldigital rectal examination undergoing their first prostate biopsy wererecruited from six medical centers. Patients with previous biopsy,prostate cancer, urinary tract infection (UTI) or prostatitis within theprior year, antibiotic use within one month, 5-� reductase inhibitor use,allergy to fluoroquinolones or clinical suspicion of UTI were excluded.Men were randomized to two weeks of ciprofloxacin 500 mg twice dailyor no antibiotic. A PSA was obtained 21-45 days following randomiza-tion and immediately prior to prostate biopsy. All patients receivedinstitution-specific prophylactic peri-procedural antibiotics. Primaryendpoint was change in PSA between baseline and on the day ofbiopsy. The trial was closed early following an interim analysis anddecision rule for futility and early stopping.

RESULTS: Complete data was available on 77 men with amean age of 60.6 (IQR: 53.8 – 66.7). In the control group (no antibiotic;n�39), mean baseline and pre-biopsy PSA were 6.5 and 6.9 ng/ml,respectively (p�0.8). In men receiving antibiotic (n�38), mean base-line and pre-biopsy (post-antibiotic) PSA were 7.6 and 8.5 ng/ml,respectively (p�0.7). Prostate cancer was detected in 36 (47%) men.Detection rates did not significantly differ between individuals with anincreasing PSA or decreasing PSA between the two measurements.

CONCLUSIONS: Empiric use of antibiotics for an elevated PSAin an asymptomatic patient is not of clinical benefit.

Source of Funding: None

Vol. 187, No. 4S, Supplement, Monday, May 21, 2012 THE JOURNAL OF UROLOGY� e437