CONCLUSIONS: Cisplatin and AR-A014418 synergisticallysuppressed UC cells viability. And AR-A014418 cancelled re-growth oflow-dose cisplatin in xenograft model.

Source of Funding: None

524LOSS OF NUCLEAR PROTHYMOSIN-�EXPRESSION INCREASESTUMOR RECURRENCE IN BLADDER CANCER WHICH ISASSOCIATED WITH LOSS OF PTEN EXPRESSION

Yuh-Shyan Tsai*, Tzong-Shin Tzai, Tainan, Taiwan;Yeong-Chin Jou, Chia-Yi, Taiwan; Hsin-Tzu Tsai, Chao-Liang Wu,Ai-Li Shiau, Tainan, Taiwan

INTRODUCTION AND OBJECTIVES: Prothymosin-�(PTMA)is a nuclear protein that is usually transported into the nucleus andinvolves many biologic functions. We previously reported aberrantPTMA expression occurs in urothelial carcinoma of the urinary bladderand loss of nuclear entry of PTMA protein, resulting in cytoplasmicaccumulation, is significantly associated with subsequent bladder tu-mor recurrence in urothelial carcinoma of upper urinary tract. The aimof this study is to investigate whether loss of nuclear PTMA expressionaffects tumors recurrence in human bladder cancer and explore itsmechanism.

METHODS: Paraffin-embedded tissues were collected from151 bladder cancer patients, treating with endoscopic resection with orwithout intravesical therapy as indicated. Immunohistochemical PTMAstaining was performed and analyzed whether PTMA expression cor-relates with clinicopathologic characteristics and patient survival or not.Three stable transfectants of human J82 bladder cancer cells express-ing either ectopic nuclear, cytoplasmic PTMA expression or vector onlywere developed for subsequent in vitro cell proliferation, migrationassays and in vivo tumorigenesis assays and mice survival in SCIDmice. Further, cDNA differential array was performed and the involvedmolecular pathways were postulated and validated with quantitativeRT-PCR assay from the frozen specimens of human bladder tumor.

RESULTS: Loss of nuclear PTMA expression, significantlyassociated with non-papillary morphology (p�0.04), grade (p�0.01),and staging (p�0.01), was an independent prognostic indicator forshort recurrence-free survival (p�0.009). Although that there were nodifferences in cell proliferation or migration assays, Mice with ectopiccytoplasmic PTMA-expressing J82 transfectants exhibited significantlymore rapid tumor growth and shorter survival than those with nuclearPTMA-expressing ones. The result from cDNA array assay of three J82transfectants showed PIK3-Akt pathway was one of the postulatedmolecular pathways. As compared with vector only transfactants, nu-clear PTMA-expressing transfectants regained PTEN, but cytoplasmicones did not, both of them were demonstrated from the qRT-PCR andwestern blotting assays. Similarly, nuclear PTMA-expressing bladdertumor specimens had significantly higher PTEN mRNA levels thanothers, as shown from qRT-PCR assay.

CONCLUSIONS: In this study we demonstrated that loss ofnuclear PTMA expression increased tumor recurrence in bladder can-cer which was associated with loss of PTEN expression.

Source of Funding: None

Kidney Cancer: Evaluation and Staging

Moderated Poster 17

Sunday, May 15, 2011 3:30 PM-5:30 PM

525SIMPLIFIED FUHRMAN GRADING SYSTEM IN CLEAR CELLRENAL CELL CARCINOMA

Sung Kyu Hong*, Chang Wook Jeong, Jong Jin Oh, Jung Soo Nam,Seongnam-si, Korea, Republic of; In Rae Cho, Koyang, Korea,Republic of; Woong Na, Seok-Soo Byun, Gheeyoung Choe,Seongnam-si, Korea, Republic of; Cheol Kwak, Hyeon Hoe Kim,Seoul, Korea, Republic of; Sang Eun Lee, Seongnam-si, Korea,Republic of

INTRODUCTION AND OBJECTIVES: Previously, several renalcell carcinoma (RCC) series have demonstrated significant prognosticdifferences among patients with RCCs of different Fuhrman gradesonly after clustering RCCs of different tumor grades into a singlecategory. Thus, we investigated the efficacy of simplified (two- orthree-tiered) Fuhrman grading systems as a prognostic indicator in acontemporary cohort of patients who received surgical management forclear cell RCC.

METHODS: We assessed and analyzed various clinicopatho-logic factors by reviewing the medical records of 431 patients whoreceived surgical management for clear cell RCC. Conventional four-tiered Fuhrman grading system was compared to a modified two-tieredgrading system (Fuhrman grades I and II were combined as one classand grades III and IV as another) and also a three-tiered gradingsystem (only grades I and II were combined). Efficacies of gradingsystems were assessed via univariate analyses and multivariate mod-els for prediction of cancer-specific survival.

RESULTS: Four-tiered and three-tiered grading system showedcomparable accuracies (76.5% vs 76.2%, p�0.614) for predicting cancer-specific survival, higher than that of two-tiered system (72.5%) in univari-ate analyses (both p�0.05). Among three aforementioned grading sys-tems, only three-tiered Fuhrman grading system was observed to be anindependent predictor of cancer-specific survival in multivariate analysis(p�0.046). When receiver operating characteristics–derived area underthe curve (AUC)s of multivariate models for predicting cancer-specificsurvivals were assessed, AUCs for a model including three-tieredFuhrman grading system and for another model including conventionalfour-tiered Fuhrman grading system were the same (95.3%), followed bythat of model incorporating two-tiered grading system (95.1%).

CONCLUSIONS: A modified version of conventional Fuhrmangrading system in which grades I and II are combined to form athree-tiered grading system was found to be an independent predictorof cancer-specific survival while showing the comparable level of pre-dictive accuracy as conventional four-tiered Fuhrman grading system inboth univariate analysis and multivariate model setting among a con-temporary cohort of clear cell RCC. Such results suggest that amodified, three-tiered Fuhrman grading system can be considered asan appropriate option in the application of nuclear grading system forthe prognostication of clear cell RCC.

Source of Funding: None

Vol. 185, No. 4S, Supplement, Sunday, May 15, 2011 THE JOURNAL OF UROLOGY� e213