1401 THE FGFR3 MUTATION IDENTIFIES PATIENTS WITH ...

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Michael A. Jewett, Toronto, Canada; Yair Lotan, Dallas, TX; Theo H. van der Kwast, Alexandre R. Zlotta, Toronto, Canada. INTRODUCTION AND OBJECTIVES: ...

Vol. 185, No. 4S, Supplement, Tuesday, May 17, 2011

THE JOURNAL OF UROLOGY姞

e561

The presence of a FGFR3 mutation was associated with lower stage (P⬍0.001), lower grade (P⬍0.001), absence of CIS (P⫽0.005), absence of LVI (P⫽0.001) and pN0 (P⫽0.003). We found no correlation for the FGFR3 mutation to gender or margin status. We found a FGFR3 mutation in 2 out of 68 analyzed positive nodes. The same mutation was detected in the RC specimen. CONCLUSIONS: The FGFR3 mutation selectively identifies patients with favorable BC at RC. The mutation was extremely rare in patients with cancer-positive nodes. FGFR3 mutation status is a promising marker to guide decision making on adjuvant therapy after RC. Source of Funding: Dutch Cancer Society and University of Toronto

1402 CANCER STEM CELL MARKER EXPRESSION IN MUSCLE-INVASIVE UROTHELIAL CARCINOMA Edward Diaz*, Christina Ching, Paul Elson, Donna Hansel, Cleveland, OH Source of Funding: Supported by a grant from the Egyptian Ministry of Higher Education via the Egyptian Cultural and Educational Bureau (ECEB) in Washington DC.

1401 THE FGFR3 MUTATION IDENTIFIES PATIENTS WITH FAVORABLE DISEASE AT RADICAL CYSTECTOMY FOR BLADDER CANCER Bas W. van Rhijn*, Amsterdam, Netherlands; Peter J. Bostrom, Toronto, Canada; Shahrokh F. Shariat, Dallas, TX; Antonio Finelli, Toronto, Canada; Arthur I. Sagalowsky, Dallas, TX; Neil E. Fleshner, Bharati Bapat, Toronto, Canada; Hannes Kortekangas, Turku, Finland; Raheela Ashfaq, Dallas, TX; Tuomas Mirtti, Turku, Finland; Michael A. Jewett, Toronto, Canada; Yair Lotan, Dallas, TX; Theo H. van der Kwast, Alexandre R. Zlotta, Toronto, Canada INTRODUCTION AND OBJECTIVES: Radical cystectomy (RC) is the standard treatment for patients with treatment-refractory non-muscle invasive (NMI) and for muscle invasive (MI) bladder cancer (BC). The FGFR3 mutation has gained attention as a marker for favorable NMI-BC and it was found to be associated with favorable prognosis. We determined the FGFR3 mutation status in a cohort of patients who underwent RC and evaluated its potential as a marker for favorable disease. METHODS: We included 290 patients from three university hospitals (Dallas, N⫽132; Toronto, N⫽104; Turku, N⫽54) who underwent radical cystectomy with at least a bilateral pelvic lymph-adenectomy. Patients who received neo-adjuvant treatment were excluded. All cases were reviewed by one uro-pathologist. FGFR3 mutation status was examined by multiplex PCR-SNaPshot analysis in the 290 cystectomy specimens and in 68 of 92 cancer-positive nodes. FGFR3 mutation status was correlated to various clinical and pathological parameters using chi-square statistics. RESULTS: A FGFR3 mutation was detected in 37 (13%) of RCs. Sixty-two patients were female. The mean age at RC was 65.5 years (range: 39 – 88 yrs). Pathological stage was ⬍pT2, pT2, pT3 and pT4 in 48, 84, 120 and 38 RCs, respectively. Grade 2 (WHO1973) was found in 64 cases and Low-grade (WHO2004) in 24 cases. The remainder of the RCs were G3 and/or High-grade. Carcinoma in situ (CIS) and lympho-vascular invasion (LVI) were found 133 (46%) and 138 (48%) times, respectively. In 92 (32%) RC, positive lymph-nodes (N1⫽30, N2⫽62) were found. The median number of removed nodes was 13 (range: 1–53). Positive surgical margins were found at the bladder in 10, at the ureter in 7 and at the urethra in 6 cases.

INTRODUCTION AND OBJECTIVES: Multiple cancer stem cell (CSC) markers have been identified for urothelial carcinoma (UCC). However, few studies have evaluated expression of these markers within benign urothelium, and few studies have correlated CSC marker expression with clinical outcome. Our objective was to compare CSC marker expression in muscle-invasive UCC and benign urothelium, and correlate CSC marker expression with clinical outcome. METHODS: 118 UCC specimens and 21 benign urothelial specimens were processed into tissue microarrays and stained with antibodies for CSC markers: CD24, CD44, CD44v6, CD47, 67LR (Laminin Receptor). Tumors were positive if ⬎5% of the cells demonstrated immunoreactivity. Expression was substratified into focal or diffuse expression. Clinical course of patients with UCC was abstracted and outcomes were correlated. RESULTS: UCC specimens revealed gross expression of CD24, CD44, CD44v6, and 67LR in 63%, 63%, 69%, and 18% of samples, respectively. Normal urothelium revealed gross expression of CD24, CD44, Cd44v6, and 67LR in 50%, 60%, 60% expressed, and 5% of samples, respectively. There were no statistically significant differences in frequency of gross expression between groups. When classifying expression pattern as either focal or diffuse it was noted that CD24, CD44, and CD44v6 expression was almost always “focal” in normal urothelium, and almost always “diffuse” in UCC (p⬍.003 in all cases). 67LR expression was diffusely expressed in both groups. Overall 35% of patients recurred (median recurrence-free survival of 30.1 months) and 64% died of disease (median survival of 22.2 months). None of the CSC markers, individually, were found to impact outcome. However, an analysis of disease subgroups (LN positive vs LN negative disease revealed a correlation between CSC marker expression and outcome. In LN negative disease a multivariable analysis revealed positive CD44v6 negatively impacted both recurrence free survival (RFS) (p⫽0.02) and overall survival (p⫽0.04), and negative 67LR expression negatively impacted RFS (p⫽0.08), and overall survival (p⫽0.008). In LN positive disease positive 67LR expression negatively impacted RFS (p⫽0.03), and overall survival (p⫽0.004). CONCLUSIONS: CSC markers CD24, CD44, and CD44v6 are expressed in higher percentages of UCC cells versus normal urothelium, suggesting enrichment of CSCs in muscle-invasive UCC. Outcomes appear to be impacted by 67LR and CD44v6 in LN negative disease, and 67LR in LN positive disease suggesting a combination of pathologic stage and CSC marker expression may help predict disease outcome Source of Funding: None

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