higher compared to benign tissue, indicating a possible role in renal carcinogenesis. Moreover, FN1 mRNA expression is a candidate bi- omarker for objective prognosis of RCC. Source of Funding: None 210 LOSS OF CHROMOSOME 3P IN CLEAR CELL RENAL CELL CARCINOMA – ARE THERE DIFFERENCES ACCORDING TO THE UNDERLYING ABERRATION? Tobias Klatte*, Nagesh Rao, Michela de Martino, Brian Shuch, Nazy Zomorodian, Jonathan Said, Fairooz Kabbinavar, Arie Belldegrun, Allan Pantuck, Los Angeles, CA INTRODUCTION AND OBJECTIVES: Loss of chromosome 3p material and subsequent loss of the von Hippel-Lindau tumor suppressor gene have been observed in about 50% of clear cell renal cell carcinomas and have been identified as a favorable prognostic factor. However, several aberrations can lead to loss of 3p material, including deletions, translocations, and inversions. The aim of this study was to assess the biologic impact of the different aberrations leading to loss of 3p. METHODS: We prospectively studied 246 consecutive patients who underwent nephrectomy for clear cell RCC at our institution. For cytogenetic analysis, viable tumor samples were collected immediately after surgery, short-term cultured and analyzed by using the GPG banding technique. The endpoint was disease-specific survival. RESULTS: Loss of 3p material was observed in 147 tumors (60%). There were 90 deletions (61%), 50 translocations (34%) and 7 inversions (5%). Tumors with loss of 3p displayed lower TNM stages and a lower frequency of sarcomatoid features than tumors without loss of 3p. There was no difference in distribution of TNM stage (p=0.336) or grade distribution (p=0.179) among the different aberrations. In univariate analysis, loss of 3p material was associated with a more favorable prognosis (p=0.028), however, among those with loss of 3p, there was no difference according to the type of aberration (p=0.541). In multivariate analysis, neither loss of 3p (p=0.779) nor the type of aberration (p=0.870) was identified as independent prognostic factor. CONCLUSIONS: Loss of chromosome 3p material is associ- ated with a more favorable prognosis among patients with clear cell renal cell carcinoma. However, the type of aberration leading to loss of 3p does not impact tumor biology. Loss of the von Hippel-Lindau tumor suppressor appears to be the crucial event in carcinogenesis, regard- less of the underlying mechanism. Source of Funding: None 211 LEVEL OF EXPRESSION AND PROGNOSTIC VALUE OF CXCL4, CXCL4L1 AND CXCR3B IN CLEAR CELL RENAL CELL CARCINOMA. Jean-Christophe Bernhard*, Fabienne Soulet, Cathy Quemener, Colette Deminiere, Patricia Fergelot, Marie Sire, Raphae ¨ l Pineau, Herve ´ Wallerand, Gilles Pasticier, Jean-Philippe Merlio, Philippe Ballanger, Alain Ravaud, Jean-Marie Ferriere, Andreas Bikfalvi, Bordeaux, France INTRODUCTION AND OBJECTIVES: The CXCL4 and CXCL4L1 chemokines and the chemokine receptor CXCR3B present angiostatic activity and tumor immunity regulation properties. We eval- uated their expression levels and their prognostic values in a clear cell Renal Cell Carcinoma (ccRCC) population. METHODS: 134 tumor and normal kidney frozen tissue sam- ples, collected from 67 patients operated for a ccRCC, were used for total RNA extraction. For each patient, q RT-PCR was performed on both tumor and normal kidney samples. mRNA levels of expression of CXCL4, CXCL4L1 and CXCR3B were determined and expression level fold changes between tumor and normal tissues were calculated. Associations between CXCL4, CXCL4L1 and CXCR3B transcript lev- els and clinicopathological parameters were determined using the Fisher exact and Kruskal-Wallis tests. Kaplan-Meier survival estimates were compared using the log rank test. RESULTS: Tumor relative sub expression was found in 65.9%, 41.5% and 19.5% of the patients for CXCL4, CXL4L1 and CXCR3B respec- tively. CXCL4 and CXCL4L1 levels of expression only, were associated to each other (p=0.0061). CXCL4 transcript level was associated with pT stage (p=0.025), Fuhrman grade (p0.01) and sinusal invasion (p=0.0349). CXCL4L1 transcript level was associated with tumor size (p=0.0273), lymph node status (p=0.0273) and Fuhrman grade (p0.01). CXCR3B transcript level was associated with tumor size (p=0.0184), lymph node status (p=0.0426) and tumor necrosis (p=0.0264). A decreasing level of CXCL4, CXCL4L1 or CXCR3B transcripts in the tumor sample was always associated with bad prognosis features such as high tumor size or grade, locally ad- vanced disease, tumor necrosis or sinusal invasion. At last follow-up (median follow-up = 13.6 months [4-31]), 11 patients (26.8%) experienced a disease progression and CXCR3B transcript level was found to impact on the Pro- gression Free survival (PFS). Median PFS was 10 months in case of low CXCR3B tumor transcript level whereas it was not reached in the group of patients with high CXCR3B level (p=0.0184). No direct significant prognostic value in terms of PFS or Cancer Specific Survival was found for CXCL4 and CXCL4L1 transcript levels. CONCLUSIONS: A low mRNA tumor level of CXCL4, CXCL4L1 and CXCR3B is associated with poor clinicopathological prognosis features. A low CXCR3B transcript level in the tumor sample is also associated with a decreased Progression Free Survival. These preliminary results encourage further investigations to assess CXCL4, CXCL4L1 and CXCR3B potential value as ccRCC biomarkers. Source of Funding: None 212 SINGLE NUCLEOTIDE POLYMORPHISMS OF MICRORNA MACHINERY GENES MODIFY THE RISK OF RENAL CELL CARCINOMA. Yohei Horikawa*, Akita, Japan; Christopher Wood, Hushan Yang, Jian Gu, Houston, TX; Tomonori Habuchi, Akita, Japan; Xifeng Wu, Houston, TX INTRODUCTION AND OBJECTIVES: MicroRNAs (miRNA) are a class of small noncoding RNA molecules that have been implicated in a wide variety of basic cellular functions through posttranscriptional regulations on their target genes. Compelling evidence has shown that miRNAs are involved in cancer initiation and progression. We hypoth- esized that genetic variations of the miRNA machinery genes could be associated with the risk of renal cell carcinoma. METHODS: We genotyped 40 single nucleotide polymor- phisms (SNP) from 11 miRNA processing genes (DROSHA, DGCR8, XPO5, RAN, DICER1, TARBP2, AGO1, AGO2, GEMIN3, GEMIN4, HIWI) and 15 miRNA genes in 279 Caucasian patients with renal cell carcinoma and 278 matched controls. RESULTS: We found that two SNPs in the GEMIN4 gene were significantly associated with altered renal cell carcinoma risks. The variant-containing genotypes of Asn929Asp and Cys1033Arg exhibited significantly reduced risks, with odds ratios (OR) of 0.67 [95% confi- dence interval (95% CI), 0.47-0.96] and 0.68 (95% CI, 0.47-0.98), respectively. Haplotype analysis showed that a common haplotype of GEMIN4 was associated with a significant reduction in the risk of renal cell carcinoma (OR, 0.66; 95% CI, 0.45-0.97). We also conducted a combined unfavorable genotype analysis including five promising SNPs showing at least a borderline significant risk association. Com- pared with the low-risk reference group with one unfavorable genotype, the median-risk and high-risk groups exhibited a 1.55-fold (95% CI, 0.96-2.50) and a 2.49-fold (95% CI, 1.58-3.91) increased risk of renal cell carcinoma, respectively (P for trend 0.001). CONCLUSIONS: Our results suggested that genetic polymor- phisms of the miRNA-machinery genes may affect renal cell carcinoma susceptibility individually and jointly. Source of Funding: None Vol. 183, No. 4, Supplement, Sunday, May 30, 2010 THE JOURNAL OF UROLOGY e83